, Volume 40, Issue 1, pp 31–74 | Cite as


A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use in Cardiovascular Disease
  • Andrew Fitton
  • Paul Benfield
Drug Evaluation



Isradipine, a dihydropyridine derivative, inhibits the inward calcium flux through ‘slow’ channels of cardiac and vascular tissue, thereby eliciting potent coronary, cerebral and peripheral vasodilatation. In comparison with other calcium channel blockers the drug offers the advantages of minimal cardiodepressant activity, a selective action on the coronary and skeletal muscle vasculature, and a prolonged vasodilatory action. Clinical trials indicate that isradipine is an effective antihypertensive agent, suitable as monotherapy or in combination with β-blockers, diuretics or ACE inhibitors, for long term treatment of mild to moderate hypertension. Preliminary findings suggest that the drug has a potential role in the treatment of chronic stable angina and, possibly, congestive heart failure. Adverse effects associated with the vasodilatory action of isradipine are generally mild, transient and well-tolerated, and are similar to those encountered with other calcium channel blockers. Thus, isradipine appears to offer a useful alternative to other dihydropyridine derivatives currently employed for the treatment of mild to moderate hypertension and, to a lesser extent, chronic stable angina. While its relative freedom from serious adverse effects may prove of value, its place in therapy vis-à-vis the established calcium channel blockers requires further clarification.

Pharmacodynamic Properties

Isradipine, in common with other calcium channel blockers, produces preferential blockade of voltage-operated calcium channels, thereby inhibiting the ‘slow’ channel influx of calcium into cardiac and vascular tissue. Its high degree of selectivity for coronary, cerebral and skeletal muscle vasculature confers potent vasodilatory activity, particularly on the arterial side of the circulation, and accounts for the drug’s pronounced antihypertensive action. In vitro animal studies indicate that isradipine has a selective depressant effect on sinoatrial node automaticity, a less pronounced inhibitory action on atrioventricular node conduction and no effect on intraventricular conduction, while its negative inotropic actions are manifest at substantially higher concentrations than its electro-physiological actions. In humans, isradipine has minimal depressant activity on sinoatrial node automaticity and negligible negative chronotropic, dromotropic and inotropic actions.

In vitro investigations in animal tissues indicate that, of the calcium channel blockers, isradipine is inferior only to nifedipine and darodipine in its coronary vasodilator potency, while its selectivity for coronary over cardiac tissues is more marked than that of nicardipine, nisoldipine, nimodipine and darodipine. Similarly, isradipine shows marked selectivity for vascular smooth muscle over cardiac tissue. In vivo animal experiments indicate that the effects of isradipine on regional circulation are consistent with the general pattern observed with other dihydropyridine derivatives (viz. increased coronary, brain and skeletal muscle blood flow and reduced renal blood flow) but are typically longer lasting.

Acute haemodynamic studies in humans suggest that isradipine induces selective arterial vasodilatation, reducing blood pressure and systemic vascular resistance without altering cardiac filling pressures, and produces secondary increases in cardiac output and stroke volume as the result of afterload reduction. Reflex tachycardia is either slight or absent, and the negative inotropic effects, which are counterbalanced by the reflex sympathetic activation associated with isradipine-induced vasodilatation, are less marked than with nifedipine. Short and long term isradipine administration is accompanied by sustained diuretic and natriuretic effects in hypertensive patients. Plasma renin activity is variously increased or unaltered by isradipine administration in these patients, and the antihypertensive efficacy of isradipine is not obviously related to pretreatment plasma renin activity.

Isradipine shows antiatherogenic effects in the cholesterol-fed rabbit at doses in the therapeutic range of human use and, moreover, does not appear to have a detrimental effect on the serum lipid profile in man. The question of whether isradipine can retard the progression of atherosclerotic lesions in humans is currently under investigation.

Pharmacokinetic Properties

Isradipine is rapidly and virtually completely absorbed from the gastrointestinal tract. It undergoes extensive first-pass hepatic metabolism, resulting in a bioavailability of approximately 17% with oral doses of 5 to 20mg. The pharmacokinetics of isradipine are linear in this dose range, and peak plasma levels (≈ 2 to 10 μg/L with capsule formulations) are attained within 2.5 hours of oral administration.

Isradipine is a lipophilic compound which is approximately 97% bound to plasma proteins (predominantly α1 -acid glycoprotein). Information regarding its tissue distribution is limited. The volume of distribution of the drug is ≈ 2.9 L/kg at steady-state.

Isradipine undergoes extensive hepatic biotransformation to yield pharmacologically inactive metabolites which remain detectable in the urine for up to 96 hours following a single oral dose. The urine: faeces excretion ratio is 70: 30, with approximately 10% of the parent compound being excreted unchanged in the faeces. Isradipine shows a biphasic elimination pattern; the effective elimination half-life of isradipine is 8.8 hours, and appears unrelated to dose.

The bioavailability of isradipine is enhanced in elderly subjects and in patients with impaired hepatic (but apparently not renal) function, indicating that dosage modification may be appropriate in these subgroups.

Therapeutic Trials

Open and placebo-controlled trials of up to 2 years duration have suggested that isradipine (typically in doses of 2.5 to 10mg twice daily) normalises systolic and diastolic blood pressure in up to 85% of patients with mild to moderate hypertension. The drug’s antihypertensive efficacy appears to be unrelated to patients’ age or race. Results from comparative studies indicate that the medium term antihypertensive efficacy pf isradipine is comparable to that of nifedipine and hydrochlorothiazide, and possibly superior to that of propranolol atenolol, prazosin and diltiazem. In combination with the β-blocker pindolol or the ACE inhibitor captopril, isradipine is effective in restoring blood pressure to normotensive levels in patients inadequately controlled by monotherapy.

Comparative trials of 4 to 6 weeks duration, albeit limited in number, have indicated that isradipine (2.5 to 7.5mg 3 times daily) is of similar efficacy to nifedipine and isosorbide dinitrate in improving exercise performance and reducing the frequency of anginal attacks in patients with chronic stable angina.

Adverse Effects

The majority of reported adverse effects of isradipine — headache, flushing, ankle oedema, dizziness and palpitations/tachycardia — are related to the drug’s vasodilatory action and are commonly encountered with other calcium channel blockers. These side effects are generally mild, dose-related and transient, occurring most frequently during the initial weeks of therapy and subsiding with continued treatment. The incidence of adverse effects with low dose isradipine therapy (≤ 5mg twice daily) is comparable to that seen with placebo, ranging from 15 to 30% of patients; facial erythema and hot flushes in particular are more frequent with higher doses (> 15 mg/day). The overall tolerability of isradipine has been assessed as good or very good in 86% of patients, and compares favourably with that of nifedipine.

Drug Interactions

Steady-state digoxin concentrations are not significantly altered by isradipine pretreatment and no special precautions appear to be necessary when the 2 drugs are jointly administered. Peak plasma propranolol concentrations are elevated by concomitant isradipine administration, although the clinical significance of this observation is unclear.

Dosage and Administration

In patients with mild to moderate hypertension, the optimum response, both with isradipine monotherapy and with β-blocker combination therapy, occurs with doses ranging from 2.5 to 7.5mg twice daily. Doses should be titrated to individual patient responses, commencing with an initial dose of 2.5mg twice daily, and dose increments should be performed at intervals of at least 4 weeks to avoid unnecessarily high doses. For patients with chronic stable angina, a regimen of isradipine 2.5 to 7.5mg 3 times daily appears appropriate.


Nifedipine Diltiazem Calcium Antagonist Nicardipine Nitrendipine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abe K, Kogure K, Watanabe T. Prevention of ischemic and postischemic brain edema by a novel calcium antagonist (PN 200-110). Journal of Cerebral Blood Flow and Metabolism 8: 436–439, 1988PubMedGoogle Scholar
  2. Abe Y, Komori T, Miura K, Takada T, Imanishi M, et al. Effects of the calcium antagonist nicardipine on renal function and renin release in dogs. Journal of Cardiovascular Pharmacology 5: 254–259, 1983PubMedGoogle Scholar
  3. Al-Mahmood HA, El-Khatim MS, Gumaa KA, Thulesius O. The effect of calcium blockers nicardipine, darodipine, PN-200-110 and nifedipine on insulin release from isolated rat pancreaticislets. Acta Physiologica Scandinavica 126: 295–298, 1986PubMedGoogle Scholar
  4. Andersson OK, Persson B, Hedner T, Aurell M, Wysocki M. Blood pressure control and haemodynamic adaptation with the dihydropyridine calcium antagonist isradipine: a controlled study in middle-aged hypertensive men. Journal of Hypertension 7: 465–469, 1989PubMedGoogle Scholar
  5. Antman EM, Stone PH, Muller JE, Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part I: Basic and clinical electrophysiologic effects. Annals of Internal Medicine 93: 875–885, 1980PubMedGoogle Scholar
  6. Arge K. An overview of safety and efficacy of nicardipine in clinical trials. American Journal of Cardiology 59 (Suppl. J): 31–35, 1987Google Scholar
  7. Aronoff GR, Sloan RS. Nitrendipine kinetics in normal and impaired renal function. Clinical Pharmacology and Therapeutics 38: 212–216, 1985PubMedGoogle Scholar
  8. Barrès C, Cerutti C, Morin B, Sassard J. Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats. British Journal of Pharmacology 93: 176–184, 1988PubMedGoogle Scholar
  9. Bhatnagar SK, Amin MMA, Al-Yusuf AR. Diabetogenic effects of nifedipine. British Medical Journal 289: 19, 1984PubMedGoogle Scholar
  10. Bijak A, Pasternac A, McPherson GA, Bevan JA. Vascular bed and vasoconstrictor-dependent selectivity of the calcium channel antagonist, PN 200-110. European Journal of Pharmacology 132: 313–317, 1986PubMedGoogle Scholar
  11. Björck S, Nyberg G, Mulec H, Granerus G, Herlitz H, et al. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. British Medical Joufnal 293: 471–474, 1986Google Scholar
  12. Blackshear JL, Orlandi C, Williams GH, Hollenberg NK. The renal response to diltiazem and nifedipine: comparison with nitroprusside. Journal of Cardiovascular Pharmacology 8: 37–43, 1986PubMedGoogle Scholar
  13. Blumlein SL, Sievers R, Kidd P, Parmley W. Mechanism of protection from atherosclerosis by verapamil in the cholesterolfed rabbit. American Journal of Cardiology 54: 884–889, 1984PubMedGoogle Scholar
  14. Bourdillon PD, Poole-Wilson PA. The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium. Circulation Research 50: 360–368, 1982PubMedGoogle Scholar
  15. Boutagy J, Rumble F, Dunagan F. Determination of isradipine and the oxidative pyridine metabolite in human plasma by high-performance liquid chromatography. Journal of Chromatography 487: 483–488, 1989PubMedGoogle Scholar
  16. Boutagy J, Rumble F, Gilmour M, Stokes G, Shenfield G. High performance liquid chromatography (HPLC) of isradipine (PN 200-110) - application to a clinical trial. Abstract no. 172. Clinical and Experimental Pharmacology and Physiology (Suppl. 11), 1987Google Scholar
  17. Braunwald E. Mechanism of action of calcium-channel-blocking agents. New England Journal of Medicine 307: 1618–1627, 1982PubMedGoogle Scholar
  18. Brister NW, Barnette RE, Schartel SA, Cavarocchi NC. Isradipine for blood pressure reduction following myocardial revascularization. Abstract. Anesthesiology 71 (Suppl. 3A): A195, 1989Google Scholar
  19. British Isradipine Hypertension Group. Evaluation of the safety and efficacy of isradipine in elderly patients with essential hypertension. American Journal of Medicine 86 (Suppl. 4A): 110–114, 1989Google Scholar
  20. Broudy DR, Greenberg BH, Siemienczuk D. Beneficial effects of the calcium antagonist PN 200-110 in patients with congestive heart failure. Journal of Cardiovascular Pharmacology 10: 190–195, 1987PubMedGoogle Scholar
  21. Bühler F, Kiowski W. Age and antihypertensive response to calcium antagonists. Journal of Hypertension 5 (Suppl. 4): 111–114, 1987Google Scholar
  22. Carruthers SG. Dynamic interaction between atenolol and the calcium blocker PN 200-110. Abstract no. 508. Acta Pharmacologica et Toxicologica 59 (Suppl. 5): 180, 1986Google Scholar
  23. Cauvin C, Hwang O, Yamamoto M, van Breemen C. Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats. American Journal of Cardiology 59: 116B-122B, 1987Google Scholar
  24. Cauvin C, Loutzenhiser R, van Breemen C. Mechanisms of calcium-antagonist induced vasodilation. Annual Review of Pharmacology and Toxicology 23: 373–396, 1983PubMedGoogle Scholar
  25. Cavero I, Boudot J-P, Feuvray D. Diltiazem protects the isolated rabbit heart from the mechanical and ultrastruptural damage produced by transient hypoxia, low flow ischemia and exposure to Ca2+ -free medium. Journal of Pharmacology and Experimental Therapeutics 226: 258–268, 1983PubMedGoogle Scholar
  26. Chandler MHH, Schran HF, Cutler RE, Smith AJ, Gonasun LM, et al. The effects of renal function on the disposition of isradipine. Journal of Clinical Pharmacology 28: 1076–1080, 1988PubMedGoogle Scholar
  27. Charles S, Ketelslegers J-M, Buysschaert M, Lambert AE. Hyperglycaemic effect of nifedipine. British Medical Journal 283: 19–20, 1981PubMedGoogle Scholar
  28. Chellingsworth MC, Willis JV, Jack DB, Kendall MJ. Pharmacokinetics and pharmacodynamics of isradipine (PN 200-110) in young and elderly patients. American Journal of Medicine 84 (Suppl, 3B): 72–79, 1988Google Scholar
  29. Chobanian AV. Treatment of the elderly hypertensive patient. American Journal of Medicine 77: 22–27, 1984PubMedGoogle Scholar
  30. Clifton GD, Blouin RA, Dilea C, Schran HF, Hassell AE, et al. The pharmacokinetics of oral isradipine in normal volunteers. Journal of Clinical Pharmacology 28: 36–42, 1988PubMedGoogle Scholar
  31. Cook NS, Hof RP. Cardioprotection by the calcium antagonist PN 200-110 in the absence and presence of cardiodepression. British Journal of Pharmacology 86: 181–189, 1985PubMedGoogle Scholar
  32. Corea L, Miele N, Bentivoglio M, Boschetti E, Agabiti-Rosei E, et al. Acute and chronic effects of nifedipine on plasma renin activity and plasma adrenaline and noradrenaline in controls and hypertensive patients. Clinical Science 57: 115S–117S, 1979PubMedGoogle Scholar
  33. Craven PA, DeRubertis FR. Ca2+ -dependent modulation of renin release from isolated glomeruli: apparent independence from alterations in cGMP. Metabolism 34: 651–657, 1985PubMedGoogle Scholar
  34. Curry DL, Bennett LL, Grodsky GM. Requirements for calciumion in insulin secretion by the perfused rat pancreas. American Journal of Physiology 214: 174–178, 1968PubMedGoogle Scholar
  35. Dacquet C, Mironneau C, Mironneau J. Effects of calcium entry blockers on calcium-dependent contractions of rat portal vein. British Journal of Pharmacology 92: 203–211, 1987PubMedGoogle Scholar
  36. Dahlöf B, Andrén L, Eggertsen R, Jern S, Svensson A, et al. The long-term effect of isradipine in pindolol-treated patients. Journal of Hypertension 5 (Suppl. 5): S567–S570, 1987PubMedGoogle Scholar
  37. Davis D, Baily RG, Deiling SM, Zelis R. Failure of tolerance to develop to the acute renal and splanchnic vasodilator effects of the calcium-blocker PN 200-110 in patients with congestive heart failure. Abstract no. 1019. Circulation 76 (Suppl. IV): 256, 1987Google Scholar
  38. DeKeyser P, Bouvé J, Clement D, Degraef R, Meurant JP, et al. Isradipine in essential hypertension: the Belgian General Practitioners’ Study. American Journal of Medicine 86 (Suppl. 4A): 103–109, 1989PubMedGoogle Scholar
  39. DeLeeuw PW, BirKenhäger WH. Effects of verapamil in hypertensive patients. Acta Medica Scandinavica (Suppl. 681): 125‐128, 1984Google Scholar
  40. Devis G, Somers G, Van Obberghen E, Malaisse WJ. Calcium antagonists and islet function.I. Inhibition by verapamil. Diabetes 2.4: 547–551, 1975Google Scholar
  41. Dietz JR, Davis JO, Freeman RH, Villarreal D, Echtenkamp SF. Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs. Hypertension 5: 482–488, 1983PubMedGoogle Scholar
  42. Drake-Holland AJ. Biochemical features of myocardial ischemia. In Protection of Tissues against Hypoxia, Wauquier A, Borgers M, Amery WK (Eds), pp. 87–93, Elsevier, Amsterdam, 1982Google Scholar
  43. Edgar B. Clinical pharmacokinetics of felodipine. Ph.D Thesis, University of Göteborg, 1988Google Scholar
  44. Eggertsen R, Svensson A, Dahlöf B, Hansson L. Additive effect of isradipine in combination with captopril in hypertensive patients. American Journal of Medicine 86 (Suppl. 4A): 124–126, 1989PubMedGoogle Scholar
  45. Etingin OR, Hajjar D. Nifedipine increases cholesteryl ester hydrolytic activity in lipid-laden rabbit arterial smooth muscle cells. Journal of Clinical Investigation 75: 1554–1558, 1985PubMedGoogle Scholar
  46. Ferlinz J, Citron PD. Hemodynamic and myocardial performance characteristics after verapamil use in congestive heart failure. American Journal of Cardiology 51: 1339–1345, 1983PubMedGoogle Scholar
  47. Fisher CA, Josephson ME, Wacht-Fogel YT, Colman RW, Addonizio VP. Verapamil and diltiazem as antiplatelet agents: Spectrum and mechanisms of activity. Circulation 68 (Suppl. III): 318, 1983Google Scholar
  48. Fleckenstein A, Frey M, Fleckenstein-Grün G. Consequences of uncontrolled calcium entry and its prevention with calcium antagonists. European Heart Journal 4 (Suppl. H): 43–50, 1983PubMedGoogle Scholar
  49. Foster TS, Hamann SR, Richards VR, Bryant PJ, Graves DA, et al. Nifedipine kinetics and bioavailability after single intravenous and oral doses in normal subjects. Journal of Clinical Pharmacology 23: 161–170, 1983PubMedGoogle Scholar
  50. Frey M, Keidel J, Fleckenstein A. Verhütung experimenteller Gefässverkalkungen (Mönckebergs Typ der Arteriosklerose) durch Calcium-Antagonisten bei Ratten. In Fleckenstein A and Roskamm H (Eds) Calcium-Antagonismus, pp. 258–285, Springer, Berlin, 1980Google Scholar
  51. Frithz G, Åström B, Dahlöf B, Hansson L, Tollin C, et al. Improved blood pressure control with isradipine in hypertensive patients treated with pindolol. American Journal of Medicine 86 (Suppl. 4A): 115–118, 1989PubMedGoogle Scholar
  52. Ginsberg R, David K, Bristow MR, McKennel K, Kodel SR, et al. Calcium antagonists suppress atherogenesis in aorta but not in intramural coronary arteries of cholesterol-fed rabbits. Laboratory Investigation 49: 154–158, 1983Google Scholar
  53. Giugliano D, Torella R, Cacciapuoti F, Gentile S, Verza M, et al. Impairment of insulin secretion in man by nifedipine. European Journal of Clinical Pharmacology 18: 395–398, 1980PubMedGoogle Scholar
  54. Gleerup G, Winther K. Differential effects of non-specific beta-blockade and calcium antagonism on blood-clotting mechanisms. American Journal of Medicine 86 (Suppl. 4A): 127–129, 1989PubMedGoogle Scholar
  55. Gobel FL, Nordstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 57: 549–556, 1978PubMedGoogle Scholar
  56. Goldstein RE, Beiser GD, Stampfer M, Epstein SE. Impairment of anatomically mediated heart rate control in patients with cardiac dysfunction. Circulation Research 36: 571–578, 1975PubMedGoogle Scholar
  57. Greenberg B, Siemienczuk D, Broudy D. Hemodynamic effects of PN 200-110 (isradipine) in congestive heart failure. American Journal of Cardiology 59: 70B-74B, 1987Google Scholar
  58. Grodsky GM, Bennett LL. Cation requirement for insulin secrein the isolated perfused pancreas. Diabetes 15: 910–913, 1966PubMedGoogle Scholar
  59. Habib JB, Bossaller C, Wells S, Williams C, Morrisett JD, et al. Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200-110. Circulation Research 58: 305–309, 1986PubMedGoogle Scholar
  60. Hamilton BP. Treatment of essential hypertension with PN 200-110 (isradipine). American Journal of Cardiology 59: 141B–145B, 1987PubMedGoogle Scholar
  61. Hamilton J, Kuzbida G, Pavlis R, Hamilton B. Isradipine, a new calcium channel blocker for mild to moderate hypertension in older blacks. Abstract. Journal of Human Hypertension 2: 281, 1988Google Scholar
  62. Hamm CW, Opie LH. Protection of infarcting myocardium by slow channel inhibitors. Circulation Research 50: 1129–1138, 1983Google Scholar
  63. Handler CE, Rosenthal E, Tsagadopoulos D, Najm Y. Comparison of isradipine and nifedipine in chronic stable angina. International Journal of Cardiology 18: 15–26, 1988PubMedGoogle Scholar
  64. Handler CE, Sowton E. Safety, tolerability and efficacy of PN 200-110, a new calcium antagonist in patients with angina and coronary heart disease. European Journal of Clinical Pharmacology 27: 415–417, 1984PubMedGoogle Scholar
  65. Handley DA, Van Valen RG, Melden MK, Saunders RN. Suppression of rat carotid lesion development by the calcium channel blocker PN 200-110. American Journal of Pathology 124: 88–93, 1986PubMedGoogle Scholar
  66. Hansson L, Dahlöf B. Antihypertensive effect of a new dihydropyridine calcium antagonist, PN 200-110 (isradipine) combined with pindolol. American Journal of Cardiology 59: 137B–140B, 1987PubMedGoogle Scholar
  67. Heider JG, Weinstein DB, Pickens CE, Lan S, Su C-M. Antiatherogenic activity of the calcium channel blocker isradipine (PN 200-110); a novel effect on matrix synthesis independent of calcium channel blockade. Transplantation Proceedings 19 (Suppl. 5): 96–101, 1987PubMedGoogle Scholar
  68. Henquin JC. Tolbutamide stimulation and inhibition of insulin release: studies of the underlying ionic mechanisms in isolated rat islets. Diabetologia 18: 151–160, 1980PubMedGoogle Scholar
  69. Henry PD, Bentley KL Suppression of atherogenesis in cholesterol-fed rabbits treated with nifedipine. Journal of Clinical In-vestigation 68: 1366–1369, 1981Google Scholar
  70. Henry PD, Shuchleib R, Davis J, Weiss ES, Sobel BE. Myocardial contracture and accumulation of mitochondrial calcium in is-chemic rabbit heart. American Journal of Physiology 223: H677–H684, 1977Google Scholar
  71. Henry PD, Wahl AM. Diltiazem and nitrendipine suppress hypoxic contracture in quiescent ventricular myocardium. European Heart Journal 4: 819–822, 1983PubMedGoogle Scholar
  72. Higuchi S, Shiobara Y. Comparative pharmacokinetics of nicardipine hydrochloride, a new vasodilator in various species. Xenobiotica 10: 447–454, 1980PubMedGoogle Scholar
  73. Hof RP. Modification of vasopressin-and angiotensin II-induced changes by calcium antagonists in the peripheral circulation of anaesthetized rabbits. British Journal of Pharmacology 85: 75–87, 1985PubMedGoogle Scholar
  74. Hof RP. Comparison of cardiodepressant and vasodilator effects of PN 200-110 (isradipine), nifedipine and diltiazem in anaesthetized rabbits. American Journal of Cardiology 59: 37B–42B, 1987aPubMedGoogle Scholar
  75. Hof R. Pharmacology of a new calcium antagonist, isradipine with target tissue selectivity. Second Cardiovascular Pharmacother-apy Symposium, October 18th 1987, San Francisco, Califor-nia, 1987bGoogle Scholar
  76. Hof RP, Evenou J-P, Hof-Miyashita A. Similar increase in circulating renin after equihypotensive doses of nitroprusside, dihydralazine or isradipine in conscious rabbits. European Journal of Pharmacology 136: 251–254, 1987aPubMedGoogle Scholar
  77. Hof RP, Hof A. The renin-angiotensin system modulates the perition pheral vascular effects of the calcium antagonist isradipine in anesthetized rabbits. Journal of Cardiovascular Pharmacology 12: 233–238, 1988PubMedGoogle Scholar
  78. Hof RP, Hof A, Neumann P. Effects of PY 108-068, a new calcium antagonist on general haemodynamics and regional blood flow in anaesthetized cats: a comparison with nifedipine. Journal of Cardiovascular Pharmacology 4: 352–362, 1982aPubMedGoogle Scholar
  79. Hof RP, Hof A, Rüegg UT, Cook NS, Vogel A. Stereoselectivity at the calcium channel: different profiles of hemodynamic activity of the enantiomers of the dihydropyridine derivative PN 200-110. Journal of Cardiovascular Pharmacology 8: 221–226, 1986PubMedGoogle Scholar
  80. Hof RP, Hof A, Scholtysik G, Menninger K. Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anaesthetized cats and dogs. Journal of Cardiovascular Pharmacology 6: 407–416, 1984aPubMedGoogle Scholar
  81. Hof RP, Hof-Miyashita A. Different peripheral vasodilator effects of isradipine in sodium-loaded and sodium-depleted rabbits. General Pharmacology 19: 243–247, 1988PubMedGoogle Scholar
  82. Hof R, Rüegg UT. Pharmacology of the new calcium antagonist isradipine and its metabolites. American Journal of Medicine 84(Suppl. 3B): 13–17, 1988Google Scholar
  83. Hof RP, Salzmann R, Siegl H. Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart. American Journal of Cardiology 59: 30B–36B, 1987bPubMedGoogle Scholar
  84. Hof RP, Scholtysik G. Effects of the calcium antagonist PY 108-068 on myocardial tissues in vitro and on reflex tachycardia in vivo. Journal of Cardiovascular Pharmacology 5: 176–183, 1983PubMedGoogle Scholar
  85. Hof RP, Scholtysik G, Loutzenhiser R, Vuorela HJ, Neumann P. PN 200-110, a new calcium antagonist: electrophysiological, inotropic and chronotropic effects on guinea pig myocardial tissue and effects on contraction and calcium uptake of rabbit aorta. Journal of Cardiovascular Pharmacology 6: 399–406, 1984bPubMedGoogle Scholar
  86. Hof RP, Vuorela HJ, Neumann P. PY 108-068, a new potent and selective inhibitor of calcium-induced contraction of rabbit aortic rings. Journal of Cardiovascular Pharmacology 4: 344–351, 1982bPubMedGoogle Scholar
  87. Holmberg S, Wieslaw S, Varnauskas E. Coronary circulation during heavy exercise in control subjects and patients with coronary heart disease. Acta Medica Scandinavica 190: 465–480, 1971PubMedGoogle Scholar
  88. Hulthén UL, Bolli P, Bühler FR. Calcium influx blockers in the treatment of essential hypertension. Acta Medica Scandinavica Suppl. 681: 101–108, 1984Google Scholar
  89. Hulthén UL, Katzman PL, Hökfelt B. Effect of long term felodipine treatment on renal vascular tone, glomerular filtration rate and renal tubular function in essential hypertension. Drugs 34 (Suppl. 3): 67–68, 1987PubMedGoogle Scholar
  90. Isradipine in Hypertension Study Group. A multicenter evaluation of the safety and efficacy of isradipine and atenolol in the treatment of hypertension. American Journal of Medicine 86 (Suppl. 4A): 119–123, 1989Google Scholar
  91. Italian-Belgian Isradipine Study Group. Multicenter evaluation of the safety and efficacy of isradipine in hypertension. American Journal of Medicine 86 (Suppl. 4A): 94–97, 1989Google Scholar
  92. Jean C, Laplanche R. Assay of isradipine and of its major metabolites in biological fluids by capillary gas chromatography and chemical ionization mass spectrometry. Journal of Chromatography 428: 61–69, 1988PubMedGoogle Scholar
  93. Jespersen LT, Krusell LR, Sihm I, Pedersen OL. Differential effects of isradipine and atenolol on peripheral hemodynamics and arterial compliance. American Journal of Medicine 86 (Suppl. 4A): 57–59, 1989PubMedGoogle Scholar
  94. Jie K, van Brummelen P, Timmermans PB, Thoolen MJ, van Zwieten PA. Effects of PN 200-110, a new calcium antagonist, on α1 - and α2 -adrenoceptor mediated vasoconstriction elicited by selective a-adrenoceptor agonists and catecholamines in the pithed rat. Archives Internationales de Pharmacodynamie et de Therapie 278: 72–86, 1985PubMedGoogle Scholar
  95. Jie K, van Brummelen P, Vermey P, Timmermans PB, Van Zwieten PA. Influence of calcium entry blockade on α1 - and α2 -adrenoceptor mediated vasoconstriction in the forearm of hypertensive patients. European Journal of Clinical Pharmacology 32: 115–120, 1987PubMedGoogle Scholar
  96. Johns EJ. The influence of diltiazem and nifedipine on renal function in the rat. British Journal of Pharmacology 84: 707–713, 1985PubMedGoogle Scholar
  97. Johnson BF, Wilson J, Marwaha R, Hoch K, Johnson J. The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics. Clinical Pharmacology and Therapeutics 42: 66–71, 1987PubMedGoogle Scholar
  98. Kates RE. Calcium antagonists: pharmacokinetic properties. Drugs 25: 113–124, 1983PubMedGoogle Scholar
  99. Katz AM, Reuter H. Cellular calcium and cardiac cell death. American Journal of Cardiology 44: 188–190, 1979PubMedGoogle Scholar
  100. Kazda S, Garthoff B, Meyer H, Schlossmann K, Stoepel K, et al. Pharmacology of a new calcium antagonistic compound, isobutyl methyl l,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate (nisoldipine, Bay K5552). Arzneimittel-Forschung 30: 2144–2162, 1980PubMedGoogle Scholar
  101. Kazda S, Knorr A, Towart R. Common properties and differences between various calcium antagonists. Progress in Pharmacology 5: 83–116, 1983Google Scholar
  102. Kinoshita M, Kusukawa R, Shimono Y, Motomura M, Tomonaga G, et al. Effects of diltiazem hydrochloride on renal hemodynamics and urinary electrolyte excretion. Japanese Circulation Journal 42: 553–560, 1978PubMedGoogle Scholar
  103. Kiowski W, Bühler FR, Fadayomi MO, Erne P, Müller FB, et al. Age, race, blood pressure and renin: predictors for antihypertensive treatment with calcium antagonists. American Journal of Cardiology 56: 81H-85H, 1985Google Scholar
  104. Kirkendall WM. Comparative assessment of first-line agents for treatment of hypertension. American Journal of Medicine 84 (Suppl. 3B): 32–41, 1988Google Scholar
  105. Klein WW. Treatment of hypertension with calcium channel blockers: European data. American Journal of Medicine 77 (Suppl. 4A): 143–146, 1984PubMedGoogle Scholar
  106. Kleinbloesem CH, Van Brummelen P, Faber H, Danhof M, Vermeulen NPE, et al. Variability in nifedipine pharmacokinetics and dynamics: a new oxidation polymorphism in man. Biochemical Pharmacology 33: 3721–3724, 1984aPubMedGoogle Scholar
  107. Kleinbloesem CH, Van Brummelen P, van de Linde JA, Voogd PJ, Breimer DD. Nifedipine: kinetics and dynamics in healthy subjects. Clinical Pharmacology and Therapeutics 35: 742–749, 1984bPubMedGoogle Scholar
  108. Kleinbloesem CH, van Brummelen P, van Harten J, Danhof M, Breimer DD. Nifedipine: influence of renal function on pharmacokinetic/hemodynamic relationship. Clinical Pharmacology and Therapeutics 37: 563–574, 1985PubMedGoogle Scholar
  109. Kohlhardt M, Fleckenstein A. Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn-Schmiedeberg’s Archives of Pharmacology 298: 267–272, 1977PubMedGoogle Scholar
  110. Krusell LR, Jespersen LT, Schmitz A, Thomsen K, Pedersen OL. Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine. Hypertension 10: 577–581, 1987PubMedGoogle Scholar
  111. Landau S, Kaminetzky JS, Hogan C, Tepper D, Tullo N, et al. Comparison of the cardiac electrophysiologic effects of isradipine and verapamil in man. Abstract no. 5. Journal of Clinical Pharmacology 28: 909, 1988Google Scholar
  112. Lasseter KC, Shamblen EC, Murdoch AA. Steady-state pharmacokinetics of nitrendipine in hepatic insufficiency. Journal of Cardiovascular Pharmacology 6: S977–S981, 1984PubMedGoogle Scholar
  113. Lee HR, Roeske WR, Yamamura HI. The measurement of free nitrendipine in human serum by an equilibrium dialysis-radio-receptor assay. Life Sciences 33: 1821–1829, 1983PubMedGoogle Scholar
  114. Ljung B. Vascular selectivity of felodipine. Drugs 29 (Suppl. 2): 46–58, 1985PubMedGoogle Scholar
  115. Loutzenhiser R, Epstein M. Effects of calcium antagonists on renal hemodynamics. American Journal of Physiology 249: F619–F629, 1985PubMedGoogle Scholar
  116. Loutzenhiser R, Epstein M. Calcium antagonists and the kidney. Hospital Practice 22: 63–76, 1987PubMedGoogle Scholar
  117. Low RI, Takeda P, Mason DT, De Maria AN. The effects of calcium channel blocking agents on cardiovascular function. American Journal of Cardiology 49: 547–553, 1982PubMedGoogle Scholar
  118. Malaisse WJ, Boschero AC. Calcium-antagonists and islet function. XI. Effect of nifedipine. Hormone Research 8: 203–209, 1977PubMedGoogle Scholar
  119. Malaisse WJ, Sener A. Calcium-antagonists and islet function. XII. Comparison between nifedipine and chemically related drugs. Biochemical Pharmacology 30: 1039–1041, 1981PubMedGoogle Scholar
  120. Margolis B, Lucas C, Henry PD. Effects of Ca++ -antagonists on platelet aggregation and secretion. Circulation 62 (Pt 2): 191, 1980Google Scholar
  121. Marre M, Misumi J, Raemsch KD, Corvol P, Menard J. Diuretic and natriuretic effects of nifedipine on isolated perfused rat kidneys. Journal of Pharmacology and Experimental Therapeutics 223: 263–270, 1982PubMedGoogle Scholar
  122. Matsumoto S, Takashi I, Toshikatsu S, Takahashi M, Su K, et al. Hemodynamic effects of nifedipine in congestive heart failure. American Journal of Cardiology 46: 476–480, 1980PubMedGoogle Scholar
  123. Mauser M, Voelker W, Ickrath O, Karsch KR. Myocardial properties of the new dihydropyridine calcium antagonist isradipine compared to nifedipine with or without additional beta blockade in coronary artery disease. American Journal of Cardiology 63: 40–44, 1989PubMedGoogle Scholar
  124. McAllister RG. Clinical pharmacokinetics of calcium channel antagonists. Journal of Cardiovascular Pharmacology 4: S340–S345, 1982PubMedGoogle Scholar
  125. McDonald RH, Corder CN, Vagnucci AH, Shuman J. The multiple factors affecting plasma renin activity in essential hypertension. Archives of Internal Medicine 138: 557–561, 1978PubMedGoogle Scholar
  126. McGrath BP, Newman R, Older P. Hemodynamic study of short-and long-term isradipine treatment in patients with chronic ischaemic congestive heart failure. American Journal of Medicine 86 (Suppl. 4A): 75–80, 1989PubMedGoogle Scholar
  127. McMahon FG, Vargas R, Ryan JR, Miller H, Faraday S. An acute dose-response pharmacodynamic evaluation of orally administered isradipine (PN 200-110) in hypertensive patients. Journal of Clinical Pharmacology 28: 664–666, 1988PubMedGoogle Scholar
  128. Midas Research Group, Furberg CD, Byington RP, Borhani NA. Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS): design features. American Journal of Medicine 86 (Suppl. 4A): 37–39, 1989PubMedGoogle Scholar
  129. Mitchell AD, Steiner TJ. Nimodipine — a calcium antagonist in stroke therapy? In Breenhalgh RM, Rose FC (Eds) Progress in Stroke Research 2. pp. 315–323, Pitman fress, Bath, UK, 1983Google Scholar
  130. Mitchell LB, Schroeder JS, Mason JW. Comparative clinical electrophysiologic effects of diltiazem, verapamil and nifedipine: a review. American Journal of Cardiology 49: 629–635, 1982PubMedGoogle Scholar
  131. Mohanty PK, Gonasun LM, Goodman RP, Kirkendall WM, Kontos HA, et al. Isradipine (PN200-110) versus hydrochlorothiazide in mild to moderate hypertension: a multicenter study. American Journal of Hypertension 1: 241S–244S, 1988PubMedGoogle Scholar
  132. Müller-Schweinitzer E, Neumann P. In vitro effects of calcium antagonists PN 200-110 nifedipine, and nimodipine on human and canine cerebral arteries. Journal of Cerebral Blood Flow and Metabolism 3: 354–361, 1983PubMedGoogle Scholar
  133. Nakao J, Ito H, Ooyama T, Chang W, Murota S. Calcium dependency of aortic smooth muscle migration induced by 12-L-hydroxy-5,8,-10,14-eicosatetraenoic acid. Atherosclerosis 46: 309–319, 1983PubMedGoogle Scholar
  134. Nayler WG. Cardioprotective effects of calcium ion antagonists in myocardial ischaemia. Clinical and Investigative Medicine 3: 91–99, 1980PubMedGoogle Scholar
  135. Nayler WG. Calcium and cell death. European Heart Journal 4 (Suppl. C): 33–41, 1983PubMedGoogle Scholar
  136. Nayler WG, Ferrari R, Williams A. Protective effect of pretreatment with verapamil nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. American Journal of Cardiology 46: 242–248, 1980PubMedGoogle Scholar
  137. Nayler WG, Grinwald P. Calcium entry blockers and myocardial function. Federation Proceedings 40: 2855–2861, 1981PubMedGoogle Scholar
  138. Nelson EB, Pool JL, Taylor AA. Antihypertensive efficacy of isradipine in humans: a new dihydropyridine calcium channel antagonist. Clinical Pharmacology and Therapeutics 40: 694–697, 1986PubMedGoogle Scholar
  139. Niederberger W, Gonasun LM, Kutz K. A population pharmacokinetic study during phase III clinical trials for the calcium antagonist PB 200-110. Third European Congress of Biopharmaceutics and Pharmacokinetics, Freiburg, Federal Republic of Germany, April 1986Google Scholar
  140. Oesterle SN, Schroeder JS. Calcium-entry blockade, beta-adrenergic blockade and the reflex control of circulation. Circulation 65: 669–670, 1982PubMedGoogle Scholar
  141. Pagani G, Lancranjan I, Marbach P, Gianola D, Pagani MD, et al. PN200-110, a new Ca++ antagonist, failed to affect GH secretion in acromegaly. Abstract 1–15. 1st European Congress of Endocrinology, June 21–25, 1987Google Scholar
  142. Parratt JR. In Parratt (Ed.) Control and manipulation of calcium movement: a biological council symposium. Raven Press, New York, 1985Google Scholar
  143. Pedersen OL, Krusell LR, Sihm I, espersen LT, Thomsen K. Long-term effects of isradipine on blood pressure and renal function. American Journal of Medicine 86 (Suppl. 4A): 15–18, 1989PubMedGoogle Scholar
  144. Persson B, Andersson OK, Wysocki M, Hedner T, Aurell M. Renal and hemodynamic effects of isradipine in essential hypertertsion. American Journal of Medicine 86 (Suppl. 4A): 60–64, 1989PubMedGoogle Scholar
  145. Pinquier JL, Urien S, Lemaire M, Chaumet-Riffaud P, Tillement JP. Comparative binding of two closely related dihydropyridines (isradipine and darodipine) to serum proteins and erythrocytes. Pharmacology 36: 305–312, 1988PubMedGoogle Scholar
  146. Pool PE, Seagren SC, Salel AF. Isradipine in the treatment of angina pectoris. American Journal of Medicine 84 (Suppl. 3B): 62–66, 1988Google Scholar
  147. Price HL. General anesthesia and circulatory homeostasis. Physiological Reviews 40: 187–218, 1960PubMedGoogle Scholar
  148. Prisant LM, Carr AA, Nelson EB, Winer N, Velasquez MT, et al. Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives. A multicenter evaluation. Archives of Internal Medicine 149: 2453–2457, 1989PubMedGoogle Scholar
  149. Raemsch KD, Sommer J. Pharmacokinetics and metabolism of nifedipine. Hypertension 5 (Suppl. II): 18–24. 1983Google Scholar
  150. Rai GS, Murphy PJ. Whole blood viscosity and calcium blockers, isradipine and nifedipine in elderly hypertensives. Journal of Drug Development 1: 221–224, 1989Google Scholar
  151. Rauramaa R, Taskinen E, Seppänen K, Rissanen V, Salonen R, et al. Effects of calcium antagonist treatment on blood pressure, lipoproteins, and prostaglandins. American Journal of Medicine 84 (Suppl. 3B): 93–96, 1988Google Scholar
  152. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wave-front phenomenon of ischemic cell death. 1. Myocardial infarct size vs. duration of coronary occlusion in dogs. Circulation 56: 786–794, 1977PubMedGoogle Scholar
  153. Rodin SM, Johnson BF, Wilson J, Ritchie P, Johnson J. Comparative effects of verapamil and isradipine on steady-state digoxin kinetics. Clinical Pharmacology and Therapeutics 43: 668–672, 1988PubMedGoogle Scholar
  154. Rouleau J-L, Parmley WW, Stevens J, Wikman-Coffelt J, Sievers R, et al. Verapamil suppresses atherosclerosis in cholesterolfed rabbits. Journal of the American College of Cardiology 1: 1453–1460, 1983PubMedGoogle Scholar
  155. Rowe JW. Approach to the treatment of hypertension in older patients. Preliminary results with isradipine. American Journal of Medicine 84 (Suppl. 3B): 46–50, 1988Google Scholar
  156. Rubin RP. The role of calcium in the release of neurotransmitter substances and hormones. Pharmacology Review 22: 389–428, 1970Google Scholar
  157. Rüegg PC, Nelson DJ. Safety and efficacy of isradipine, alone and in combination, in the treatment of angina pectoris. American Journal of Medicine 86 (Suppl. 4A): 70–74, 1989PubMedGoogle Scholar
  158. Rüegg UT, Doyle VM, Hof RP. Effects of calcium entry blockers on calcium fluxes in a vascular smooth muscle cell line. Journal of Hypertension 3 (Suppl. 3): S57–S59, 1985PubMedGoogle Scholar
  159. Rupoli L, Fruscio M, Gradnik R, Chianca R, Leonetti G, et al. Cardiovascular and renal effects of single administration of three different doses of isradipine in hypertensive patients. American Journal of Medicine 86 (Suppl. 4A): 65–66, 1989PubMedGoogle Scholar
  160. Ryan M, Jain A, Wallin D, Clifton G, McMahon FG, et al. Comparative effects of isradipine and enalapril on renal hemodynamics in essential hypertension. Abstract no. II-D-3. Clinical Pharmacology and Therapeutics 45: 160, 1989Google Scholar
  161. Sakanashi M, Miyamoto Y, Noguchi K, Kato T, Matsuzaki T, et al. Cardiovascular effects of the new calcium antagonist isradipine and of diltiazem in anesthetized open-chest dogs. Arzneimittel-Forschung 38: 1792–1796, 1988aPubMedGoogle Scholar
  162. Sakanashi M, Noguchi K, Miyamoto Y, Kato T, Nagamine F, et al. Comparative effects of the calcium antagonist isradipine and some other dihydropyridine derivatives on regional blood flow in anesthetized open-chest dogs. Archives Internationales de Pharmacodynamic et de Therapie 294: 159–174, 1988bGoogle Scholar
  163. Saltiel E, Ellrodt AG, Monk JP, Langley MS. Felodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 36: 387–428, 1988PubMedGoogle Scholar
  164. Samuel P, Kirkendall W, Schaefer EJ, Chin B, Schoenfeld BH, et al. Effects of isradipine, a new calcium antagonist, versus hydrochlorothiazide on serum lipids and apolipoproteins in patients with systemic hypertension. American Journal of Cardiology 62: 1068–1071, 1988PubMedGoogle Scholar
  165. Sando H, Katagiri H, Okada M, Shoda R, Arai Y, et al. The effect of nifedipine and nicardipine on glucose tolerance, insulin and C-peptide. Abstract. Diabetes 32: 66A, 1983Google Scholar
  166. Satoh K, Kawada M, Wada Y, Taira N. Cardiovascular actions of the dihydropyridine calcium antagonist nimodipine in the dog. Arzneimittel-Forschung 34: 563–568, 1984PubMedGoogle Scholar
  167. Satoh K, Yanagisawa T, Taira N. Mechanisms underlying the cardiovascular action of a new dihydropyridine vasodilator Yc-93. Clinical and Experimental Pharmacology and Physiology 7: 249–262, 1980PubMedGoogle Scholar
  168. Sauter A, Rudin M. Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging. Stroke 17: 1228–1234, 1986PubMedGoogle Scholar
  169. Sauter A, Rudin M. Effects of calcium-antagonists on high energy phosphates in ischemic rat brain measured by 3l P NMR spectroscopy. Magnetic Resonance in Medicine 4: 1–8, 1987PubMedGoogle Scholar
  170. Sauter A, Rudin M, Wiederhold K-H, Hof RP. Cerebrovascular, biochemical, and cytoprotective effects of isradipine in laboratory animals. American Journal of Medicine 86 (Suppl. 4A): 134–146, 1989PubMedGoogle Scholar
  171. Schachter M. Do calcium antagonists affect platelets? European Heart Journal 8 (Suppl. K): 75–82, 1987PubMedGoogle Scholar
  172. Scheidt S. The role of calcium blockers in the treatment of chronic stable angina. In Flaim SF & Zelis R (Eds) Calcium blockers: mechanisms of action and clinical applications, pp. 231–244, Urban & Schwarzenberg, Baltimore-Munich, 1982Google Scholar
  173. Scher AM, Young AC. Reflex control of heart rate in the unanesthetized dog. American Journal of Physiology 218: 780–789, 1970PubMedGoogle Scholar
  174. Scholtysik G, Schaad A. Cardiac cellular electrophysiology as a tool to prove Ca++ slow channel inhibition by PY 108-068. Triangle 21: 49–55, 1983Google Scholar
  175. Schran HF, Jaffe JM, Gonasun LM. Clinical pharmacokinetics of isradipine. American Journal of Medicine 84 (Suppl. 3B): 80–89, 1988Google Scholar
  176. Schran HF, Shepherd AM, Choc MM, Gonasun LM, Brodie CL. The effect of concomitant administration of isradipine and propranolol on their steady-state bioavailability. Abstract. Pharmacologist 31: 153, 1989Google Scholar
  177. Schulman SP, Gerstenblith G. Hypertension in the elderly: treatment. Cardiology Clinics 4: 245–252, 1986PubMedGoogle Scholar
  178. Shand DG. Biological determinants of altered pharmacokinetics in the elderly. Gerontology 28 (Suppl. 1): 8–17, 1982PubMedGoogle Scholar
  179. Shaw AM, Brydon LJ, Maclntyre DE. PAF-induced human platelet aggregation is selectively inhibited by class II and class III, but not class I calcium ‘antagonists’. European Heart Journal 4 (Suppl. B): 4, 1983Google Scholar
  180. Shen AC, Jennings RB. Myocardial calcium and magnesium in acute ischemic injury. American Journal of Pathology 67: 417–440, 1972PubMedGoogle Scholar
  181. Shepherd AMM, Brodie CL, Carrillo DW, Kwan CM. Pharmacokinetic interaction between isradipine and propranolol. Abstract no. IVB-1, Clinical Pharmacology and Therapeutics 43: 194, 1988Google Scholar
  182. Shepherd AMM, Carr A, Davidoff M, Hamilton J, Schnaper H, et al. PN 200-110: gradual onset of antihypertensive action? Abstract no. PIID-4, Clinical Pharmacology and Therapeutics 41: 187, 1987Google Scholar
  183. Shepherd AMM, Carr AA, Davidov M, Hamilton J, Schnaper H, et al. Efficacy and safety of isradipine in hypertension. Journal of Cardiovascular Pharmacology 13: 580–585, 1989PubMedGoogle Scholar
  184. Sieber C, del Pozo E. Failure of a new calcium-antagonist PN 200-110 and nifedipine to affect exercise stimulated GH-secretion in healthy volunteers. Hormone and Metabolic Research 19: 281–282, 1987PubMedGoogle Scholar
  185. Siejö BK. Cell damage in the brain: a speculative synthesis. Journal of Cerebral Blood Flow and Metabolism 1: 155–185, 1981Google Scholar
  186. Simonsen K, Sundstedt CD. Dose-response relationship and incidence of adverse drug reactions with isradipine in patients with essential hypertension. American Journal of Medicine 86 (Suppl. 4A): 91–93, 1989PubMedGoogle Scholar
  187. Singh BN. Pharmacological basis for the therapeutic applications of slow-channel blocking drugs. Angiology-Journal of Vascular Diseases 33: 492–515, 1982Google Scholar
  188. Singh BN, Ellrodt G, Nademanee K. Calcium antagonists: cardiocirculatory effects and therapeutic applications. In Hurst JW (Ed.) Clinical Essays on the Heart, Vol. 2, pp. 65–97, McGraw-Hill, New York, 1984Google Scholar
  189. Singh BN, Nademanee K, Baky SH. Calcium antagonists: clinical use in the treatment of arrhythmias. Drugs 25: 125–153, 1983PubMedGoogle Scholar
  190. Smith SA, Young MA, Littler WA. Renal effects of nicardipine in essential hypertension. Abstract no. 41. Journal of Hypertension 5 (Suppl. 5): S640, 1987Google Scholar
  191. Sobel BE. Calcium antagonists in cardiovascular therapeutics. Practical Cardiology 7: 1–8, 1981Google Scholar
  192. Sørensen SS, Thomsen OO, Danielsen H, Pedersen EB. Effect of verapamil on renal plasma flow, glomerular filtration rate, plasma angiotensin II, aldosterone and arginine vasopressin in essential hypertension. European Journal of Clinical Pharmacology 29: 257–261, 1985PubMedGoogle Scholar
  193. Sorkin EM, Clissold SP, Brogden RN. Nifedipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs 30: 182–274, 1985PubMedGoogle Scholar
  194. Staessen J, Fagard R, Lijnen P, Amery A. Acute effects of isradipine on angiotensin II responsiveness. American Journal of Medicine 84 (Suppl. 3B): 67–71, 1988Google Scholar
  195. Staessen J, Lijnen P, Fagard R, Hespel P, Tan WP, et al. Effects of the new calcium entry blocker isradipine (PN 200-110) in essential hypertension. Journal of Cardiovascular Pharmacology 13: 271–276, 1989PubMedGoogle Scholar
  196. Stein GH, Lopez L, Quay G, McCarley D, Matthews K. Long-term improvement of lipid profiles with isradipine in elderly hypertensive patients. Abstract no. 1030. American Journal of Hypertension 2 (No. 5 Part 2): 8A, 1989Google Scholar
  197. Stein O, Leitersdorf E, Stein Y. Verapamil enhances receptor-mediated endocytosis of low density lipoprotcins by aortic cells in culture. Arteriosclerosis 5: 35–44, 1985PubMedGoogle Scholar
  198. Stone PH, Antman EM, Muller JE, Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: hemodynamic effects and clinical applications. Annals of Internal Medicine 93: 886–904, 1980PubMedGoogle Scholar
  199. Stone PH, Muller JE, Turi ZG, Geltman E, Jaffe AS, et al. Efficacy of nifedipine therapy in patients with refractory angina pectoris: significance of the presence of coronary vasospasm. American Heart Journal 106: 644–652, 1983PubMedGoogle Scholar
  200. Strauss HC, Saroff AL, Bigger JT, Giardina ECG. Premature atrial stimulation as a key to the understanding of sinoatrial conduction in man. Circulation 47: 86–93, 1973PubMedGoogle Scholar
  201. Sundstedt CD, Rüegg PC, Keller A, Waite R. A multicenter evaluation of the safety, tolerability and efficacy of isradipine in the treatment of essential hypertension. American Journal of Medicine 86 (Suppl. 4A): 98–102, 1989PubMedGoogle Scholar
  202. Swartz SL. Antihypertensive and hormonal effects of PN 200-110, a new calcium channel blocker, in essential hypertension. Journal of Clinical Hypertension 3: 463–469, 1987PubMedGoogle Scholar
  203. Taira N. Effects of diltiazem and other calcium-antagonists on cardiac functions and coronary blood flow as assessed in blood-perfused dog-heart preparations. In Bing RJ (Ed.) New drug therapy with a calcium antagonist, Diltiazem Hakone Symposium ’78, pp. 91–103, Excerpta Medica, Amsterdam, 1979Google Scholar
  204. Taira N. Differences in cardiovascular profile among calcium antagonists. American Journal of Cardiology 59: 24B-29B, 1987Google Scholar
  205. Taira N, Kawada M, Satoh K. Cardiac versus vasodilator actions of KB-944, a new calcium antagonist, assessed in isolated, blood-perfused heart preparations of the drug. Journal of Cardiovascular Pharmacology 5: 349–356, 1983PubMedGoogle Scholar
  206. Taylor SH, Jackson NC, Allen J, Pool PE. Efficacy of a new calcium antagonist PN 200-110 (isradipine) in angina pectoris. American Journal of Cardiology 59: 123B-129B, 1987Google Scholar
  207. Théroux P, Taeymans Y, Waters DD. Calcium antagonists. Clinical use in the treatment of angina. Drugs 25: 178–195, 1983PubMedGoogle Scholar
  208. Tse F, Jaffe J. Pharmacokinetics of PN 200-110 after single and repeated oral doses in man. Abstract no. 494. Acta Pharmacologica et Toxicologica 59 (Suppl. 5): 176, 1986Google Scholar
  209. Tse FLS, Jaffe JM. Pharmacokinetics of PN 200-110 (isradipine), a new calcium antagonist, after oral administration in man. European Journal of Clinical Pharmacology 32: 361–365, 1987PubMedGoogle Scholar
  210. Underwood SM, Feneck RO, Davies SW, Walesby RK, Lunnon MW. Use of isradipine in hypertension following coronary artery bypass surgery. American Journal of Medicine 86 (Suppl. 4A): 81–87, 1989PubMedGoogle Scholar
  211. Urien S, Pinquier J-L, Paquette B, Chaumet-Riffaud P, Kiechel J-R, et al. Effect of the binding of isradipine and darodipine to different plasma proteins on their transfer through the rat blood-brain barrier. Drug binding to lipoproteins does not limit the transfer of drug. Journal of Pharmacology and Experimental Therapeutics 242: 349–354, 1987PubMedGoogle Scholar
  212. van den Berg EK, Dehmer GJ. Acute hemodynamic effects of intravenous isradipine. American Journal of Cardiology 61: 1102–1105, 1988aPubMedGoogle Scholar
  213. van den Berg EK, Dehmer GJ. A comparison of the effects of intravenous isradipine and verapamil on coronary and systemic hemodynamics in man. Abstract. Journal of the American College of Cardiology 11: 242A, 1988bGoogle Scholar
  214. van den Toren EW, vanBruggen A, Ruegg PC, Lie KI. Hemodynamic effects of an intravenous infusion of isradipine in patients with congestive heart failure. American Journal of Medicine 84 (Suppl. 3B): 97–101, 1988Google Scholar
  215. van Wijk LM, van den Toren EW, van Gelder I, Crijns HJ, Ruegg P, et al. Electrophysiologic properties of isradipine (PN 200-110) in humans. Journal of Cardiovascular Pharmacology 14: 492–495, 1989PubMedGoogle Scholar
  216. Vatner SF, Braunwald E. Cardiovascular control mechanisms in the conscious state. New England Journal of Medicine 293: 970–976, 1975PubMedGoogle Scholar
  217. Vermeulen A, Wester A, Willemse PFA, Lustermans FAT, Stegeman CJ, et al. Comparison of isradipine and diltiazem in the treatment of essential hypertension. American Journal of Medicine 84 (Suppl. 3B): 42–45, 1988Google Scholar
  218. Wada Y, Satoh K, Taira N. Coronary vasodilator compared to cardiac effects of PY 108-068, a new dihydropyridine vasodilator, on isolated, blood-perfused dog-heart preparations. Journal of Cardiovascular Pharmacology 6: 881–887, 1984PubMedGoogle Scholar
  219. Wada Y, Satoh K, Taira N. Separation of the coronary vasodilator from the cardiac effects of PN 200-110, a new dihydropyridine calcium antagonist, in the dog heart. Journal of Cardiovascular Pharmacology 7: 190–196, 1985PubMedGoogle Scholar
  220. Weinstein DB, Heider JG. Antiatherogenic properties of calcium antagonists. American Journal of Cardiology 59: 163B-172B, 1987Google Scholar
  221. Weiss K, Fitscha P, O’Grady J, Sinzinger H. Isradipine: a potent calcium blocker with beneficial effects on platelet function and vascular prostacyclin production. Thrombosis Research 54: 311–317, 1989PubMedGoogle Scholar
  222. Welzel D, Burger KJ, Weidinger G. Calcium antagonists as first-line antihypertensive agents: a placebo-controlled, comparative trial of isradipine and nifedipine. Journal of Cardiovascular Pharmacology 15 (Suppl. 1): S70–S74, 1990PubMedGoogle Scholar
  223. Winer N, Thys-Jacobs S, Kumar R, Davidson WD, Grayson M, et al. Evaluation of isradipine (PN 200-110) in mild to moderate hypertension. Clinical Pharmacology and Therapeutics 42: 442–448, 1987PubMedGoogle Scholar
  224. Winniford MD, Willerson JT, Hillis LD. Calcium antagonists in the treatment of individuals with ischemic heart disease. Angiology 33: 522–539, 1982PubMedGoogle Scholar
  225. Wit AL, Cranefield P. Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanisms by which it arrests re-entrant atrioventricular nodal tachycardia. Circulation Research 35: 413–425, 1974PubMedGoogle Scholar
  226. Wollheim CB, Sharp GWG. Regulation of insulin release by calcium. Physiological Reviews 61: 914–973, 1981PubMedGoogle Scholar
  227. Yasute H, Omote S, Takizawa A, Nagao M, Miwa K, et al. Exertional angina pectoris is caused by coronary arterial spasm: effects of various drugs. American Journal of Cardiology 43: 647–652, 1979Google Scholar
  228. Zipes DP, Besch HP, Watanabe AM. Role of the slow current in cardiac electrophysiology. Circulation 51: 761–766, 1975PubMedGoogle Scholar
  229. Zipes DP, Fischer JC. Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in the dog. Circulation Research 34: 184–192, 1974PubMedGoogle Scholar

Copyright information

© Adis International Limited 1990

Authors and Affiliations

  • Andrew Fitton
    • 1
  • Paul Benfield
    • 1
  1. 1.Adis Drug Information ServicesAucklandNew Zealand

Personalised recommendations