Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Jun;27(6):763–770. doi: 10.1111/j.1365-2125.1989.tb03438.x

Pharmacodynamic and pharmacokinetic study of propranolol in patients with cirrhosis and portal hypertension.

P Calès 1, D Grasset 1, A Ravaud 1, C Meskens 1, M Blanc 1, J P Vinel 1, J Cotonat 1, J P Pascal 1
PMCID: PMC1379803  PMID: 2569324

Abstract

1. The aim of this study was to investigate the pharmacokinetics and the beta-adrenoceptor blocking activity according to time of conventional (C) and long acting (LA) propranolol in cirrhotic patients. Twenty-four patients with alcoholic cirrhosis and oesophageal varices were randomly assigned to receive either 160 mg C propranolol, 160 mg LA propranolol or placebo acutely and then following repeated administration (acute and chronic phases). Thereafter propranolol concentrations and beta-adrenoceptor blockade (resting and exercise heart rates) were measured at different intervals. 2. The Cmax was significantly higher with C propranolol in both phases. The time of Cmax was significantly later with LA propranolol in both phases. The AUCs were significantly higher after chronic administration with both formulations of propranolol. 3. The exercise peaks of beta-adrenoceptor blockade were similar between the two formulations and between the two phases of administration of propranolol. The duration of effective beta-adrenoceptor blockade was significantly longer in the chronic phase and seemed to be longer with LA than with C propranolol although this was not significant (72 +/- 31 vs 48 +/- 18 h, respectively). 4. There was a significant correlation between the log propranolol concentration and exercise heart rate but not with resting heart rate. No correlation could be demonstrated between pharmacological data and the Child Pugh score. 5. We conclude that in cirrhotic patients exercise testing was a reliable method in the assessment of beta-adrenoceptor blockade. Pharmacology of propranolol was found to be different according to the formulation or to the phase of administration.

Full text

PDF
763

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aellig W. H. beta-Adrenoceptor blocking activity and duration of action of pindolol and propranolol in healthy volunteers. Br J Clin Pharmacol. 1976 Apr;3(2):251–257. doi: 10.1111/j.1365-2125.1976.tb00600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arthur M. J., Tanner A. R., Patel C., Wright R., Renwick A. G., George C. F. Pharmacology of propranolol in patients with cirrhosis and portal hypertension. Gut. 1985 Jan;26(1):14–19. doi: 10.1136/gut.26.1.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbare J. C., Poupon R. E., Jaillon P., Prod'homme S., Darnis F., Poupon R. Y. Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis. J Hepatol. 1985;1(3):253–259. doi: 10.1016/s0168-8278(85)80053-2. [DOI] [PubMed] [Google Scholar]
  4. Blanc M., Cales P., Grasset D., Ravaud A., Meskens C., Cotonat J., Pascal J. P. Etude des paramètres de biodisponibilité du propranolol chez des malades cirrhotiques après administration orale de la forme retard. Therapie. 1987 Mar-Apr;42(2):187–191. [PubMed] [Google Scholar]
  5. Branch R. A., James J., Read A. E. A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)-propranolol. Br J Clin Pharmacol. 1976 Apr;3(2):243–249. doi: 10.1111/j.1365-2125.1976.tb00599.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coltart D. J., Shand D. G. Plasma propranolol levels in the quaniitative assessment of beta-adrenergic blockade in man. Br Med J. 1970 Sep 26;3(5725):731–734. doi: 10.1136/bmj.3.5725.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hager W. D., Pieniaszek H. J., Jr, Perrier D., Mayersohn M., Goldberger V. Assessment of beta blockade with propranolol. Clin Pharmacol Ther. 1981 Sep;30(3):283–290. doi: 10.1038/clpt.1981.161. [DOI] [PubMed] [Google Scholar]
  8. Jennings G., Nelson L., Nestel P., Esler M., Korner P., Burton D., Bazelmans J. The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity. Circulation. 1986 Jan;73(1):30–40. doi: 10.1161/01.cir.73.1.30. [DOI] [PubMed] [Google Scholar]
  9. Jirón M. I., Delhotal B., Lebrec D. Relationship between dose, blood level and haemodynamic response in patients with cirrhosis receiving propranolol. Eur J Clin Pharmacol. 1985;28(3):353–355. doi: 10.1007/BF00543337. [DOI] [PubMed] [Google Scholar]
  10. Kornhauser D. M., Wood A. J., Vestal R. E., Wilkinson G. R., Branch R. A., Shand D. G. Biological determinants of propranolol disposition in man. Clin Pharmacol Ther. 1978 Feb;23(2):165–174. doi: 10.1002/cpt1978232165. [DOI] [PubMed] [Google Scholar]
  11. Leahey W. J., Neill J. D., Varma M. P., Shanks R. G. Comparison of the efficacy and pharmacokinetics of conventional propranolol and a long acting preparation of propranolol. Br J Clin Pharmacol. 1980 Jan;9(1):33–40. doi: 10.1111/j.1365-2125.1980.tb04793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leaman D. M., Levenson L. W., Shiroff R. A., Babb J. D., DeJoseph R. L., Hayes A. H., Zelis R. Persistence of biologic activity after disappearance of propranolol from the serum. J Thorac Cardiovasc Surg. 1976 Jul;72(1):67–72. [PubMed] [Google Scholar]
  13. McAinsh J., Baber N. S., Smith R., Young J. Pharmacokinetic and pharmacodynamic studies with long-acting propranolol. Br J Clin Pharmacol. 1978 Aug;6(2):115–121. doi: 10.1111/j.1365-2125.1978.tb00835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mills P. R., Rae A. P., Farah D. A., Russell R. I., Lorimer A. R., Carter D. C. Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension. Gut. 1984 Jan;25(1):73–78. doi: 10.1136/gut.25.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mullane J. F., Kaufman J., Dvornik D., Coelho J. Propranolol dosage, plasma concentration, and beta blockade. Clin Pharmacol Ther. 1982 Dec;32(6):692–700. doi: 10.1038/clpt.1982.225. [DOI] [PubMed] [Google Scholar]
  17. Neve K. A., Molinoff P. B. Effects of chronic administration of agonists and antagonists on the density of beta-adrenergic receptors. Am J Cardiol. 1986 Apr 25;57(12):17F–22F. doi: 10.1016/0002-9149(86)90883-0. [DOI] [PubMed] [Google Scholar]
  18. Pascal J. P., Cales P. Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med. 1987 Oct 1;317(14):856–861. doi: 10.1056/NEJM198710013171403. [DOI] [PubMed] [Google Scholar]
  19. Pine M., Favrot L., Smith S., McDonald K., Chidsey C. A. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris. Circulation. 1975 Nov;52(5):886–893. doi: 10.1161/01.cir.52.5.886. [DOI] [PubMed] [Google Scholar]
  20. Poynard T., Lebrec D., Hillon P., Sayegh R., Bernuau J., Naveau S., Chaput J. C., Klepping C., Rueff B., Benhamou J. P. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding. Hepatology. 1987 May-Jun;7(3):447–451. doi: 10.1002/hep.1840070306. [DOI] [PubMed] [Google Scholar]
  21. Pugh R. N., Murray-Lyon I. M., Dawson J. L., Pietroni M. C., Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–649. doi: 10.1002/bjs.1800600817. [DOI] [PubMed] [Google Scholar]
  22. Serlin M. J., Orme M. L., MacIver M., Green G. J., Sibeon R. G., Breckenridge A. M. The pharmacodynamics and pharmacokinetics of conventional and long-acting propranolol in patients with moderate hypertension. Br J Clin Pharmacol. 1983 May;15(5):519–527. doi: 10.1111/j.1365-2125.1983.tb02085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Watson R. G., Bastain W., Larkin K. A., Hayes J. R., McAinsh J. A., Shanks R. G. A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls. Br J Clin Pharmacol. 1987 Oct;24(4):527–535. doi: 10.1111/j.1365-2125.1987.tb03207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wilson M., Morgan G., Morgan T. The effect on blood pressure of beta-adrenoceptor blocking drugs administered once daily and their duration of action when therapy is ceased. Br J Clin Pharmacol. 1976 Oct;3(5):857–861. doi: 10.1111/j.1365-2125.1976.tb00638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wood A. J., Carr K., Vestal R. E., Belcher S., Wilkinson G. R., Shand D. G. Direct measurement of propranolol bioavailability during accumulation to steady-state. Br J Clin Pharmacol. 1978 Oct;6(4):345–350. doi: 10.1111/j.1365-2125.1978.tb00862.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wood A. J., Kornhauser D. M., Wilkinson G. R., Shand D. G., Branch R. A. The influence of cirrhosis on steady-state blood concentrations of unbound propranolol after oral administration. Clin Pharmacokinet. 1978 Nov-Dec;3(6):478–487. doi: 10.2165/00003088-197803060-00005. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES