Clinical Drug Investigation

, Volume 21, Issue 1, pp 59–66 | Cite as

Pharmacokinetics of Valsartan in Hypertensive Patients on Long-Term Haemodialysis

  • Michael F. Leidig
  • Christian Delles
  • Christian Kuchenbecker
  • Rainer-Ainer-Max Lederle
  • Gottfried Weidinger
  • Roland E. Schmieder
Clinical Pharmacokinetics



Previous studies have indicated no relationship between renal function (creatinine clearance) and the pharmacokinetics of valsartan in patients with moderately impaired renal function. There are no pharmacokinetic data available for valsartan in patients on long-term haemodialysis.


To examine the pharmacokinetics of valsartan 80mg in hypertensive patients on long-term haemodialysis. Secondary objectives were to evaluate the efficacy and tolerability of valsartan in this patient group.


Multicentre, nonblind, parallel-group study.


20 hypertensive patients with no renal impairment and 20 hypertensive patients on long-term haemodialysis.


All patients were treated with valsartan 80mg once daily for 15 days. After the first dose of valsartan and at the end of the treatment period, plasma concentrations of valsartan were determined over 24 hours.


Significant differences in the area under the concentration-time curve from zero to 24 hours (AUC24h) at steady state were found between the patients on haemodialysis and those with normal renal function. In contrast, no differences were found for AUC24h during first-dose pharmacokinetics or for maximum plasma concentration and elimination half-life during first-dose and steady-state pharmacokinetics. Blood pressure decreased significantly in both groups, but the reduction in systolic blood pressure was greater in patients on haemodialysis (18mm Hg) than in the control group (6mm Hg). Valsartan 80mg was well tolerated in patients undergoing haemodialysis.


The pharmacokinetic characteristics of valsartan are altered in patients on haemodialysis under steady-state conditions, but not after single-dose administration. The increased bioavailability at steady state was still in the range of the bioavailability for the approved dose of up to 160mg in patients with or without renal impairment. Valsartan 80 mg/day was well tolerated in this patient population.


Hypertensive Patient Renal Impairment Valsartan Normal Renal Function Polycystic Kidney Disease 
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.



This study was supported in part by a grant from Novartis Pharma GmbH.


  1. 1.
    Criscione L, Bradley WA, Bühlmayer P, et al. Valsartan: preclinical and clinical profile of an antihypertensive angiotensin-II antagonist. Cardiovasc Drug Rev 1995; 230–50Google Scholar
  2. 2.
    De Gasparo M, Whitebread S. Binding of valsartan to mammalian AT1 receptors. Regul Pept 1995; 59: 303–11CrossRefGoogle Scholar
  3. 3.
    Mueller P, Cohen T, de Gasparo M, et al. Angiotensin II receptor blocakade with single doses of valsartan in healthy, normotensive subjects. Eur J Clin Pharmacol 1994; 47: 231–45CrossRefGoogle Scholar
  4. 4.
    Criscone L, de Gasparo M, Bühlmayer P, et al. Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the Ang II AT1-receptor subtype. Br J Pharmacol 1993, 110:761–71CrossRefGoogle Scholar
  5. 5.
    Pool J, Oparil S, Hedner T, et al. Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II-receptor blocker. Clin Ther 1998; 20(6): 1106–14PubMedCrossRefGoogle Scholar
  6. 6.
    Czendlik CH, Sioufi A, Preiswerk G, et al. Pharmacokinetic and pharmacodynamic interaction of single doses of valsartan and atenolol. Eur J Clin Pharmacol 1997; 52(6): 451–9PubMedCrossRefGoogle Scholar
  7. 7.
    Benz JR, Black HR, Graff A, et al. Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing therapy with monotherapy. J Hum Hypertens 1998; 12: 861–6PubMedCrossRefGoogle Scholar
  8. 8.
    Markham A, Goa KL. Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. Drugs 1997; 54(2): 299–311PubMedCrossRefGoogle Scholar
  9. 9.
    Oparil S, Dyke S, Harris F, et al. The efficacy and safety of valsartan compared with placebo in the treatment of patients with essential hypertension. Clin Ther 1996; 18(5): 797–810PubMedCrossRefGoogle Scholar
  10. 10.
    Hegner G, Faust G, Freytag F, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared to hydrochlorothiazide. Eur J Clin Pharmacol 1997; 52(3): 173–7PubMedCrossRefGoogle Scholar
  11. 11.
    Thuermann PA, Kenedi P, Schmidt A, et al. Influence of the angiotensin II antagonist valsartan on the left ventricular hypertrophy in patients with essential hypertension. Circulation 1998; 98: 2037–42CrossRefGoogle Scholar
  12. 12.
    Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial — the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–7PubMedCrossRefGoogle Scholar
  13. 13.
    Flesch G, Müller Ph, Lloyd P. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol 1997; 52: 115–20PubMedCrossRefGoogle Scholar
  14. 14.
    Waldmeier F, Flesch G, Mueller P, et al. Pharmacokinetics, disposition and biotransformation of (14C)-radiolabelled valsartan in healthy male volunteers after a single oral dose. Xenobiotica 1997; 27(1): 59–71PubMedCrossRefGoogle Scholar
  15. 15.
    Brookman LJ, Rolan PE, Benjamin IS, et al. Pharmacokinetics of valsartan in patients with liver disease. Clin Pharmacol Ther 1997; 62: 272–8PubMedCrossRefGoogle Scholar
  16. 16.
    Colussi DM, Parisot C, Rossolino ML, et al. Protein binding in plasma of valsartan, a new angiotensin II receptor antagonist. J Clin Pharmacol 1997; 37: 214–21PubMedGoogle Scholar
  17. 17.
    Mueller P, Flesch G, de Gasparo M, et al. Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects. Eur J Clin Pharmacol 1997; 52(6): 441–9CrossRefGoogle Scholar
  18. 18.
    Prasad P, Mangat S, Choi L, et al. Effect of renal function on the pharmacokinetics of valsartan. Clin Drug Invest 1997; 13: 207–14CrossRefGoogle Scholar
  19. 19.
    Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41PubMedCrossRefGoogle Scholar
  20. 20.
    Brunner LA, Powell ML, Degen P, et al. A semiautomated analytical method for the determination of potential antihypertensive agents (CGP 48933 and/or CGP 48369) in human plasma using HPLC. Lab Robot Automat 1994; 6: 171–9Google Scholar
  21. 21.
    Sioufi A, Marfil F, Godbillon J. Automated determination of an angiotensin II receptor antagonist CGP 48933, in plasma by high-performance liquid chromatography. J Liqu Chromatogr 1994; 17: 2179–86CrossRefGoogle Scholar
  22. 22.
    Czendlik CH, Sioufi A, Preiswerk G, et al. Pharmacokinetic and pharmacodynamic interaction of single doses of valsartan and atenolol. Eur J Clin Pharmacol 1997; 52: 451–9PubMedCrossRefGoogle Scholar
  23. 23.
    Plum J, Bunten B, Nemeth R, et al. Effects of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure and hypertension. J Am Soc Nephrol 1998; 9(12): 2223–34PubMedGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Michael F. Leidig
    • 1
  • Christian Delles
    • 1
  • Christian Kuchenbecker
    • 2
  • Rainer-Ainer-Max Lederle
    • 3
  • Gottfried Weidinger
    • 4
  • Roland E. Schmieder
    • 1
  1. 1.Department of Medicine IV/NephrologyUniversity of Erlangen-NürnbergNürnbergGermany
  2. 2.Physician in Private PracticeWeimarGermany
  3. 3.Physician in Private PracticeDortmundGermany
  4. 4.Novartis Pharma GmbHNürnbergGermany

Personalised recommendations