Summary
Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggest that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Acocella, G., L. Bonollo, M. Garimoldi, M. Mainardi, T. Tenconi, F. B. Nicolis: Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease. Gut13, 47–53 (1972)
Andreasen, P. B., L. Ranek, B. E. Statland, N. Tygstrup: Clearance of antipyrin-dependence of quantitative liver function. Europ. J. clin. Invest.4, 129–134 (1974)
Breimer, D. D., C. Honhoff, W. Zilly, E. Richter, J. M. van Rossum: Pharmacokinetics of hexobarbital in man after intravenous infusion. J. Pharmacokin. Biopharm.3, 1–11 (1975a)
Breimer, D. D., J. M. van Rossum: Rapid and sensitive gaschromatographic determination of hexobarbital in plasma of man using a nitrogen detector. J. Chromatogr.88, 235–243 (1974)
Breimer, D. D., W. Zilly, E. Richter: Pharmacokinetics of hexobarbital in acute hepatitis and after apparent recovery. Clin. Pharmacol. Ther.18, 433–440 (1975b)
Earnest, D. L.: The effect of phenobarbital on pruritus and bile salt kinetics in patients with biliary cirrhosis and elevated bile salt concentrations. In: Bile acids in human diseases, pp. 145–151. Stuttgart: Schattauer 1972
Held, H., R. Eisert, H. F. von Oldershausen: Pharmakokinetik von Glymidine (Glycodiazin) und Tolbutamid bei akuten und chronischen Leberschäden. Arzneimittel-Forsch. (Drug Res.)23, 1801–1807 (1973)
Jezequel, A. M., F. Orlandi, L. T. Tenconi: Changes of the smooth endoplasmic reticulum induced by rifampicin in human and guinea-pig hepatocytes. Gut12, 984–987 (1971)
Klotz, U., G. R. Avant, A. Hoyumpa, S. Schenker, G. R. Wilkinson: The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J. clin. Invest.55, 347–359 (1975)
Loo, J. C. K., S. Riegelman: Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J. pharm. Sci.59, 53–55 (1970)
Mawer, G. E., N. E. Miller, L. A. Turnberg: Metabolism of amylobarbitone in patients with chronic liver disease. Brit. J. Pharmacol.44, 549–560 (1972)
Metreau, J. M., H. Bismuth, D. Franco, D. Dhumeaux: Effect of phenobarbital in a case of extrahepatic cholestasis. Gastroenterology68, 567–571 (1975)
Rossum, J. M. van: Significance of pharmacokinetics for drug design and the planning of dosage regimens. In: Drug design, vol. I, pp. 469–521, New York: Academic Press 1971
Schoene, B., R. A. Fleischmann, H. Remmer, H. F. v. Oldershausen: Determination of drug metabolizing enzymes in needle biopsies of human liver. Europ. J. clin. Pharmacol.4, 65–73 (1972)
Spingler, H.: Über eine Möglichkeit zur colorimetrischen Bestimmung von N-(4-Methyl-benzolsulfonyl)-N′-butyl-Harnstoff im Serum. Klin. Wschr.10, 533–535 (1957)
Stiehl, A., M. M. Thaler, W. H. Admirand: The effects of phenobarbital on bile salts and bilirubin in patients with intrahepatic and extrahepatic cholestasis. New. Engl. J. Med.286, 858–861 (1972)
Thaler, M. M.: Effect of phenobarbital on hepatic transport and excretion of131J-Rose Bengal in children with cholestasis. Pediat. Res.6, 100–110 (1972)
Thomson, P. D., K. L. Melman, J. A. Richardson, K. Cohn, W. Steinbrunn, R. Cudihee, M. Rowland: Lidocaine pharmacokinetics in advanced heart failure, liver disease and renal failure in humans. Ann. int. Med.78, 499–508 (1973)
Wilcoxon, F.: Some rapid approximate statistical procedures. American Cyanamid Co., Stanford, Conn., 1949. Software Wang, Scientific Routines
Zilly, W., D. D. Breimer, E. Richter: Induction of drug metabolism in man following rifampicin treatment measured by increased hexobarbital and tolbutamide clearance. Europ. J. clin. Pharmacol.9, 219–227 (1975a)
Zilly, W., H. Wernze, D. Buchenau, D. D. Breimer, E. Richter: Einfluß von Rifampicin auf die metabolische Clearance von Galaktose und Antipyrin im Vergleich zu Hexobarbital. Verh. dtsch. Ges. inn. Med.81, 1677–1680 (1975b).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zilly, W., Breimer, D.D. & Richter, E. Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance. Eur J Clin Pharmacol 11, 287–293 (1977). https://doi.org/10.1007/BF00607679
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00607679