Summary
The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6β-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated.
Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged.
The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved.
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Skolnik JL, Stoler BS, Katz DB, Anderson WH (1976) Rifampicin, oral contraceptives, and pregnancy. JAMA 236: 1382
Bolt HM, Bolt M, Kappus H (1977) Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man. Acta Endocrinol 85: 189–197
Back DJ, Breckenridge AM, Crawford F, MacIver M, Orme ME, Park BK, Rowe PH, Smith E (1979) The effect of rifampicin on norethisterone pharmacokinetics. Eur J Clin Pharmacol 15: 193–197
Ohnhaus EE, Studer H (1983) A link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol 15: 71–76
Coert A, Geelen J, de Visser J, Van der Vies J (1975) The pharmacology and metabolism of testosterone undecanoat (TU): a new orally active androgen. Acta Endocrinol 79: 789–800
Breier CH, Drexel H, Lisch HJ, Mühlberger V, Herold M, Knapp E, Braunsteiner H (1985) Essential role of post-heparin lipoprotein lipase activity and of plasma testosterone in coronary artery disease. Lancet I: 1242–1244
Vermeulen A, Verdonck L, Van der Straeten M, Orie N (1969) Capacity of the testosterone-binding globulin in human plasma and influence of specific binding of testosterone on its metabolic clearance rate. J Clin Endocrinol 29: 1470–1480
Eichelbaum M, Spannbrucker N (1977) Rapid and sensitive method for the determination of antipyrine in biological fluids by high pressure liquid chromatography. J Chromatogr 140: 288–299
Park BK, Ohnhaus EE (1983) Urinary 6β-hydroxycortisol: a simple, non-invasive index of enzyme induction in man. Ärztl Lab 29: 53–58
Sanghvi A, Taddeini L, Wight C (1973) Determination of 17-hydroxycorticosteroids with p-hydrazino-sulfonic-phosphoric acid. Anal Chemistry 45: 207–210
De Lacerda L, Kowarski A, Johanson AJ, Athanasion R, Migeon CJ (1973) Integrated concentration and circadian variation of plasma testosterone in normal men. J Clin Endocrinol Metab 37: 366–371
Nieschlag E, Mauss J, Coert A, Kicivic P (1975) Plasma androgen levels in men after oral administration of free testosterone. Acta Endocrinol 79: 366–374
Ohnhaus EE, Breckenridge AM, Park Bk (1989) Urinary excretion of 6β-hydroxycortisol and the time course measurement of enzyme induction in man. Eur J Clin Pharmacol 36: 39–46
Shiverick KT, Neims AH (1979) Multiplicity of testosterone hydroxylases in a reconstituted cytochrome P-450 system from un-induced male rats. Drug Metab Disposit 7: 290–295
Gonzalez FJ (1989) The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288
Nocke-Finck L, Breuer H (1981) Effect of rifampicin on the biosynthesis of testosterone in rat testis. Acta Endocrinol 96: 573–576
Nocke-Finck L, Breuer H, Reimers D (1980) Wirkung von Rifampicin und Streptomycin auf die Konzentrationen von Testosteron und Cortisol in Blut von Männern. J Clin Chem Clin Biochem 18: 897–899
Brodie MJ, Boobis AR, Gill M, Mashiter K (1981) Does rifampicin increase serum levels of testosterone and oestradiol by inducing sex hormone binding globulin capacity? Br J Clin Pharmacol 12: 431–433
Butt WR (1976) Hormone chemistry, 2nd ed, Vol 2. Ellis Horwood Ltd, Chichester
Nebert CW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fuji-Kuriyame Y, Gonzalez FJ, Guengerich FP, Gunslus IC, Johnson EF, Loper JC, Sato R, Waterman MR, Waxman DJ (1991) The P450 superfamily: Update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 10: 1–14
Yanase T, Sanders D, Shibata A, Nobuo M, Simpson ER, Waterman MR (1990) Combined 17a-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P450-17a (cyp17) gene. J Clin Endocrinol Metab 70: 1325–1329
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Bammel, A., van der Mee, K., Ohnhaus, E.E. et al. Divergent effects of different enzyme-inducing agents on endogenous and exogenous testosterone. Eur J Clin Pharmacol 42, 641–644 (1992). https://doi.org/10.1007/BF00265929
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DOI: https://doi.org/10.1007/BF00265929