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Clinical Drug Investigation

, Volume 10, Issue 6, pp 337–343 | Cite as

Disposition, Elimination and Haemodynamic Effects of Gallopamil in Patients with Fatty Liver Disease

  • Martin Siepmann
  • Boinpally Ramesh Rao
  • Wilhelm Kirch
Clinical Pharmacology
  • 6 Downloads

Summary

Twenty-one hypertensive patients were treated orally with 50mg gallopamil in a sustained-release formulation once daily for 1 week. 11 patients had a normal liver function (antipyrine clearance 41.2 ± 2.8 ml/min; mean ± SD), while 10 patients had fatty liver disease (antipyrine clearance 32.3 ± 1.4 ml/min). Maximum plasma concentrations of gallopamil were 15.2 (7.9 to 29.3) µg/L (geometric mean; 95% confidence interval) in patients with normal and 16.8 (8.7 to 32.5) µg/L in those with impaired hepatic function (p > 0.05). The elimination half-life was 8.8 hours in patients with normal liver function and 9.2 hours in patients with fatty liver disease (median, p > 0.05). No significant differences were found between patients with and without concomitant liver disease with regard to the effects of gallopamil on heart rate, PQ-time and blood pressure. First degree AV-block developed during treatment with gallopamil in one patient with fatty liver disease and in another with normal liver function. The AV-block in the patient with impaired hepatic function was considered to be severe (PQ-time 270ms). In conclusion, kinetic parameters of patients with fatty liver disease did not differ significantly from those of subjects with normal liver function.

Keywords

Nifedipine Fatty Liver Disease Antipyrine Drug Invest 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.

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References

  1. 1.
    Brogden RN, Benfield P. Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in ischaemic heart disease. Drugs 1994; 47: 93–115PubMedCrossRefGoogle Scholar
  2. 2.
    Eichelbaum M. Pharmakokinetik und Metabolismus von Gallopamil. Zeitschrift für Kardiologie 1989; 78 Suppl. 5: 20–4PubMedGoogle Scholar
  3. 3.
    Stieren B, Bühler V, Hege HG, et al. Pharmacokinetics and metabolism of gallopamil. In: Kaltenbach M, Hopf R, editors. Gallopamil, pharmacological and clinical profile of a calcium antagonist. Berlin: Springer, 1984: 88–93Google Scholar
  4. 4.
    Eichelbaum M, Mikus G. Pharmacokinetics, bioavailability, cardiovascular and biochemical effects of gallopamil in patients with liver cirrhosis and in healthy subjects without liver disease. Internal Report, Dr M. Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany, 1992: 1–9Google Scholar
  5. 5.
    Kaim AAH, Farker K. Pharmacokinetics and pharmacodynamics of gallopamil in patients with liver cirrhosis [abstract no. 36]. Naunyn Schmiedebergs Arch Pharmacol 1992; 345 Suppl.: R9Google Scholar
  6. 6.
    Mensink CK, Hempenius J, Wilkens G, et al. Determination of gallopamil and norgallopamil in human plasma by high performance liquid chromatography and fluorescence detection. Description and validation of assay method. Internal Report, Pharma Bio-Reasearch International, Zuidlaren, Netherlands, 1990Google Scholar
  7. 7.
    Eichelbaum M, Somogyi A. Rapid and sensitive method for the determination of antipyrine in biological fluids by high pressure liquid chromatography. J Chromatogr 1977; 140: 288–92CrossRefGoogle Scholar
  8. 8.
    Sachs L. Angewandte Statistik. 7th ed. Berlin: Springer, 1992Google Scholar
  9. 9.
    Dylewicz P, Kirch W, Santos SR, et al. Bioavailability and elimination of nitrendipine in liver disease. Eur J Clin Pharmacol 1987; 32: 563–8PubMedCrossRefGoogle Scholar
  10. 10.
    Kleinbloesem CH, Van Harten J, Wilson JPH, et al. Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after i.v. and oral administration. Clin Pharmacol Ther 1986; 40: 21–8PubMedCrossRefGoogle Scholar
  11. 11.
    Lasseter KC, Shambleu EC, Murdoch AA, et al. Steady state pharmacokinetics of nitrendipine in hepatic insufficiency. J Cardiovasc Pharmacol 1984; 6 Suppl. 7: 977–81Google Scholar
  12. 12.
    Somogyi A, Albrecht M, Kliems G, et al. Pharmacokinetics, bioavailability and ECG response of verapamil in patients with liver cirrhosis. Br J Clin Pharmacol 1981; 12: 51–60PubMedCrossRefGoogle Scholar
  13. 13.
    Branch RA, James J, Read AE. A study of factors influencing drug disposition in chronic liver disease, using the model (+)-propranolol. Br J Clin Pharmacol 1976; 3: 243–9PubMedCrossRefGoogle Scholar
  14. 14.
    Kirch W, Rose I, Demers HG, et al. Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. Clin Pharmacokinet 1987; 13: 110–3PubMedCrossRefGoogle Scholar
  15. 15.
    Kirch W, Halabi A, Nokhodian A. Disposition and elimination of bunazosin in chronic liver disease and renal insufficiency. Eur J Drug Metab Pharmacokinet 1993; 18: 309–13PubMedCrossRefGoogle Scholar
  16. 16.
    Vesell ES, Passananti GT, Glenwright PA, et al. Studies on the disposition of antipyrine, aminopyrine, and phenacetin using plasma, saliva and urine. Clin Pharmacol Ther 1975; 18: 259–72PubMedGoogle Scholar
  17. 17.
    Andreasen PB, Ranek L, Statland BE, et al. Clearance of antipyrine-dependence of quantitative liver function. Eur J Clin Invest 1974; 4: 129–34PubMedGoogle Scholar
  18. 18.
    Andreasen PB, Vesell ES. Comparison of plasma levels of antipyrine, tolbutamide, and warfarin after oral and intravenous administration. Clin Pharmacol Ther 1974; 16: 1059–65PubMedGoogle Scholar
  19. 19.
    Williams RL, Schary WL, Blaschke TF, et al. Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin. Clin Pharmacol Ther 1976; 20: 90–7PubMedGoogle Scholar
  20. 20.
    Shull HJ, Wilkinson GR, Johnson R, et al. Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 1976; 84: 420–5PubMedGoogle Scholar
  21. 21.
    Kirch W, Ohnhaus EE, Dylewicz P, et al. Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency. Am Heart J 1986; 111: 325–9PubMedCrossRefGoogle Scholar
  22. 22.
    Storstein L. Studies on digitalis II — The influence of renal function on the renal excretion of digitoxin and its cardioactive metabolites. Clin Pharmacol Ther 1974; 16: 25–34PubMedGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Martin Siepmann
    • 1
  • Boinpally Ramesh Rao
    • 1
  • Wilhelm Kirch
    • 1
  1. 1.Institute of Clinical Pharmacology and Therapeutics, Medical SchoolUniversity of TechnologyDresdenGermany

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