The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-β-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-β-hydroxycortisol, but the magnitude of the effects was signifiantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Armitage P, Hills M (1982) The two period cross-over trial. Statistician 31: 119–131
Back DJ, Breckenridge AM, Crawford F, Maciver M, Orme ML'E, Park BK, Rowe PH, Smith E (1979) The effect of rifampicin on norethisterone pharmacokinetics. Eur J Clin Pharmacol 15: 193–197
Bolt HM, Kappus H, Bolt M (1975) Effect of rifampicin treatment on the metabolism of oestradiol and 17-ethynyloes-tradiol by human liver microsomes. Eur J Clin Pharmacol 8: 301–307
Breimer DD, Zilly W, Richter E (1977) Influence of rifampicin on drug metabolism: differences between hexobarbital and antipyrine. Clin Pharmacol Ther 21: 470–481
Brodie MJ, Boobis AR, Dollery CT, Hillyard CJ, Brown DJ, MacJntyre I, Park BK (1980) Rifampicin and vitamin D metabolism. Clin Pharmacol Ther 27: 810–814
Danhof M, Krom D, Breimer DD (1980) Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. Xenobiotica 9: 695–702
Della Bruna C, Schioppacassi C, Ungheri D, Jabes D, Morvillo E, Sanfilippo E (1983) LM 427, a new spiropiperidyl rifamycin: in vitro and in vivo studies. J Antibiot (Tokyo) 36: 1502–1506
Eichelbaum M, Spahnbrucker N (1977) Rapid and sensitive method for the determination of antipyrine in biological fluids by high pressure liquid chromatography. J Chromatogr 140: 288–292
Eichelbaum M, Sonntag B, Dengler HJ (1981) HPLC determination of antipyrine metabolites. Pharmacology 23: 192–202
Hastings RC, Jacobson RR (1983) Activity of ansamycin against Mycobacterium leprae in mice. Lancet 2: 1079–1080
Heifets LB, Eiseman MD (1985) Determination of in vitro susceptibility of Mycobacteria to ansamycin. Am Rev Respir Dis 132: 710–711
Ohnhaus EE, Park BK (1979) Measurement of urinary 6-β-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of microsomal enzyme inducing capacity of antipyrine, phenobarbitone and rifampicin. Clin Pharmacol Ther 15: 139–145
Ohnhaus EE, Kirchof B, Peheim E (1979) Effect of enzyme induction on plasma lipids using antipyrine, phenobarbitone and rifampicin. Clin Pharmacol Ther 25: 591–597
Park BK (1978) A direct radioimmunoassay for 6-β-hydroxycortisol in human urine. Steroid Biochem 9: 963–966
Perucca E (1978) Clinical consequences of microsomal enzyme induction by antiepileptic drugs. Pharmacol Ther 2: 285–314
Roots I, Holbe R, Hovermann W, Nigam S, Heinemeyer G, Hildebrandt AG (1979) Quantitative determination by HPLC of urinary 6-β-hydroxycortisol, an indicator of enzyme induction by rifampicin and antiepileptic drugs. Eur J Clin Pharmacol 16: 63–71
Sanghvi A, Wight C, Parikh B, Desai H (1973) Urinary 17-hydroxycorticosteroid determination with p-hydrazinobenzensulfonic acid phosphoric acid. Am J Clin Pathol 60: 684–690
Szasz G (1969) A kinetic photometric method for serum gamma-gamma-glutamyl-transpeptidase. Clin Chem 15: 124–136
Syvalahti EK, Pihlajamaki KK, Iisalo EJ (1974) Rifampicin and drug metabolism. Lancet 2: 232–233
Teunissen MWE, Joeres RP, Vermeulen NPE, Breimer DD (1983) Influence of 9-hydroxyellipticine and 3-methyl-cholanthrene treatment on in vivo antipyrine metabolite formation in rats. Xenobiotica 13: 223–231
Teunissen MWE, Bakker W, Meerburg-Van der Torren JE, Breimer DD (1984) Influence of rifampicin treatment on antipyrine clearance and metabolite formation in patients with tuberculosis. Br J Clin Pharmacol 18: 701–706
Toverud EL, Boobis AR, Brodie MJ, Murray S, Bennett PN, Whitmarsh V, Davies DS (1981) Differential induction of antipyrine metabolism by rifampicin. Eur J Clin Pharmacol 21: 155–160
Woodley CL, Kilburn JO (1982) In vitro susceptibility of Mycobacterium Avium Complex and Mycobacterium tubercolosis strains to a spiropiperidyl rifamycin. Am Rev Respir Dis 126: 586–587
Zilly W, Breimer DD, Richter E (1975) Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance. Eur J Clin Pharmacol 9: 219–227
Zilly W, Breimer DD, Richter E (1977) Pharmacokinetic interactions with rifampicin. Clin Pharmacokinet 2: 61–70
About this article
Cite this article
Perucca, E., Grimaldi, R., Frigo, G.M. et al. Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects. Eur J Clin Pharmacol 34, 595–599 (1988). https://doi.org/10.1007/BF00615223
- microsomal enzyme induction
- healthy volunteers
- antimicrobial agent