Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1983 Nov;16(5):565–569. doi: 10.1111/j.1365-2125.1983.tb02218.x

Induction of propranolol metabolism by rifampicin.

R J Herman, K Nakamura, G R Wilkinson, A J Wood
PMCID: PMC1428059  PMID: 6639842

Abstract

The effect of rifampicin on the blood concentration-time curve of propranolol at steady-state following oral administration of 120 mg every 8 h was investigated in six normal, young, male subjects. After an initial 2 week dosing period, all individuals additionally received 600 mg rifampicin daily for 3 weeks followed by a 4 week period during which again only the propranolol was given. In four of the subjects the effects of 900 and 1200 mg rifampicin daily was also studied. Changes in disposition were assessed by estimation of propranolol's oral clearance and elimination half-life during the dosage interval. Rifampicin (600 mg/day) caused a large increase in propranolol's oral clearance (35.7 +/- 16.3 vs 96.1 +/- 26.9 ml min-1 kg-1, mean +/- s.d.), but neither the elimination half-life nor extent of plasma binding were affected. Increasing the daily dosage to 900 and 1200 mg did not cause any additional changes in oral clearance. Four weeks after discontinuing rifampicin, propranolol's oral clearance had essentially returned to its pre-induction level. The oral clearance of propranolol was significantly smaller (89.5 +/- 14.4%) during the dosage interval immediately after administration of the last rifampicin dose than the value measured 24 h later. The findings are consistent with rifampicin causing induction of the drug metabolizing enzymes responsible for propranolol's biotransformation. The marked reduction in the steady-state propranolol blood concentration that results from chronic rifampicin administration would be expected to result in a significant change in clinical effectiveness of the beta-adrenoceptor blocker when the two drugs are used concurrently.

Full text

PDF
565

Selected References

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

  1. Bai S. A., Abramson F. P. Interactions of phenobarbital with propranolol in the dog. 1. Plasma protein binding. J Pharmacol Exp Ther. 1982 Sep;222(3):589–594. [PubMed] [Google Scholar]
  2. Bennett P. N., John V. A., Whitmarsh V. B. Effect of rifampicin on metoprolol and antipyrine kinetics. Br J Clin Pharmacol. 1982 Mar;13(3):387–391. doi: 10.1111/j.1365-2125.1982.tb01390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breckenridge A., Orme M. L., Davies L., Thorgeirsson S. S., Davies D. S. Dose-dependent enzyme induction. Clin Pharmacol Ther. 1973 Jul-Aug;14(4):514–520. doi: 10.1002/cpt1973144part1514. [DOI] [PubMed] [Google Scholar]
  4. Breimer D. D., Zilly W., Richter E. Influence of rifampicin on drug metabolism: differences between hexobarbital and antipyrine. Clin Pharmacol Ther. 1977 Apr;21(4):470–481. doi: 10.1002/cpt1977214470. [DOI] [PubMed] [Google Scholar]
  5. Chiou W. L. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J Pharmacokinet Biopharm. 1978 Dec;6(6):539–546. doi: 10.1007/BF01062108. [DOI] [PubMed] [Google Scholar]
  6. Cleaveland C. R., Shand D. G. Effect of route of administration on the relationship between -adrenergic blockade and plasma propranolol level. Clin Pharmacol Ther. 1972 Mar-Apr;13(2):181–185. doi: 10.1002/cpt1972132181. [DOI] [PubMed] [Google Scholar]
  7. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  8. Feely J., Wilkinson G. R., Wood A. J. Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med. 1981 Mar 19;304(12):692–695. doi: 10.1056/NEJM198103193041202. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Kreek M. J., Garfield J. W., Gutjahr C. L., Giusti L. M. Rifampin-induced methadone withdrawal. N Engl J Med. 1976 May 13;294(20):1104–1106. doi: 10.1056/NEJM197605132942008. [DOI] [PubMed] [Google Scholar]
  11. Levy R. H. Time-dependent pharmacokinetics. Pharmacol Ther. 1982;17(3):383–397. doi: 10.1016/0163-7258(82)90022-5. [DOI] [PubMed] [Google Scholar]
  12. Miguet J. P., Mavier P., Soussy C. J., Dhumeaux D. Induction of hepatic microsomal enzymes after brief administration of rifampicin in man. Gastroenterology. 1977 May;72(5 Pt 1):924–926. [PubMed] [Google Scholar]
  13. Nitti V., Delli Veneri F., Ninni A., Meola G. Rifampicin blood serum levels and half-life during prolonged administration in tuberculous patients. Chemotherapy. 1972;17(2):121–129. doi: 10.1159/000220845. [DOI] [PubMed] [Google Scholar]
  14. Ohnhaus E. E., Park B. K. Measurement of urinary 6-beta-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol. 1979 Mar 26;15(2):139–145. doi: 10.1007/BF00609878. [DOI] [PubMed] [Google Scholar]
  15. Ohnhaus E. E., Studer H. A link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol. 1983 Jan;15(1):71–76. doi: 10.1111/j.1365-2125.1983.tb01466.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Piafsky K. M., Borgá O., Odar-Cederlöf I., Johansson C., Sjöqvist F. Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma alpha1 acid glycoprotein. N Engl J Med. 1978 Dec 28;299(26):1435–1439. doi: 10.1056/NEJM197812282992604. [DOI] [PubMed] [Google Scholar]
  17. Piafsky K. M. Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet. 1980 May-Jun;5(3):246–262. doi: 10.2165/00003088-198005030-00004. [DOI] [PubMed] [Google Scholar]
  18. Routledge P. A., Stargel W. W., Finn A. L., Barchowsky A., Shand D. G. Lignocaine disposition in blood in epilepsy. Br J Clin Pharmacol. 1981 Nov;12(5):663–666. doi: 10.1111/j.1365-2125.1981.tb01286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schneck D. W., Pritchard J. F., Gibson T. P., Vary J. E., Hayes A. H., Jr Effect of dose and uremia on plasma and urine profiles of propranolol metabolites. Clin Pharmacol Ther. 1980 Jun;27(6):744–755. doi: 10.1038/clpt.1980.105. [DOI] [PubMed] [Google Scholar]
  20. Sotaniemi E. A., Anttila M., Pelkonen R. O., Järvensivu P., Sundquist H. Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity. Clin Pharmacol Ther. 1979 Aug;26(2):153–161. doi: 10.1002/cpt1979262153. [DOI] [PubMed] [Google Scholar]
  21. Tiula E., Neuvonen P. J. Antiepileptic drugs and alpha 1-acid glycoprotein. N Engl J Med. 1982 Oct 28;307(18):1148–1148. doi: 10.1056/NEJM198210283071813. [DOI] [PubMed] [Google Scholar]
  22. Toverud E. L., Boobis A. R., Brodie M. J., Murray S., Bennett P. N., Whitmarsh V., Davies D. S. Differential induction of antipyrine metabolism by rifampicin. Eur J Clin Pharmacol. 1981;21(2):155–160. doi: 10.1007/BF00637517. [DOI] [PubMed] [Google Scholar]
  23. Vestal R. E., Kornhauser D. M., Hollifield J. W., Shand D. G. Inhibition of propranolol metabolism by chlorpromazine. Clin Pharmacol Ther. 1979 Jan;25(1):19–24. doi: 10.1002/cpt197925119. [DOI] [PubMed] [Google Scholar]
  24. Vu V. T., Bai S. A., Abramson F. P. Interactions of phenobarbital with propranolol in the dog. 2. Bioavailability, metabolism and pharmacokinetics. J Pharmacol Exp Ther. 1983 Jan;224(1):55–61. [PubMed] [Google Scholar]
  25. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wood M., Shand D. G., Wood A. J. Altered drug binding due to the use of indwelling heparinized cannulas (heparin lock) for sampling. Clin Pharmacol Ther. 1979 Jan;25(1):103–107. doi: 10.1002/cpt1979251103. [DOI] [PubMed] [Google Scholar]
  28. Zacest R., Koch-Weser J. Relation of propranolol plasma level to beta-blockade during oral therapy. Pharmacology. 1972;7(3):178–184. doi: 10.1159/000136287. [DOI] [PubMed] [Google Scholar]
  29. Zilly W., Breimer D. D., Richter E. Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance. Eur J Clin Pharmacol. 1975 Dec 19;9(2-3):219–227. doi: 10.1007/BF00614021. [DOI] [PubMed] [Google Scholar]
  30. Zilly W., Breimer D. D., Richter E. Pharmacokinetic interactions with rifampicin. Clin Pharmacokinet. 1977 Jan-Feb;2(1):61–70. doi: 10.2165/00003088-197702010-00005. [DOI] [PubMed] [Google Scholar]
  31. van den Broek J. M., Teunissen M. W., Breimer D. D. Induction of hexobarbital and antipyrine metabolism by rifampicin treatment in the pig. Drug Metab Dispos. 1981 Nov-Dec;9(6):541–544. [PubMed] [Google Scholar]

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

RESOURCES