The effect of 2 different drug combinations on liver microsomal activity was investigated in healthy volunteers by administering antipyrine 1200 mg and phenobarbitone 100 mg, or the same dose of antipyrine with rifampicin 600 mg daily for 14 days. The effect of rifampicin 1200 mg given for only 8 days was also studied. Before and after each drug regimen, estimates were made of the total body clearance of antipyrine, γ-glutamyl-transferase (γ-GT) and urinary excretion of 6-β-hydroxycortisol as in vivo parameters of liver microsomal enzyme activity. Following combined antipyrine and phenobarbitone administration, the antipyrine clearance was increased by 80%, after antipyrine with rifampicin by 128%, and after rifampicin alone by 104%. 6-β-hydroxycortisol, corrected for 17-hydroxycorticosteroids, increased from 2.6% to 8% following antipyrine plus phenobarbitone, from 4.4% to 27.9% following antipyrine plus rifampicin, and from 5.4% to 29.7% after rifampicin given alone. Based on previous studies, antipyrine given with phenobarbitone produced slightly more induction than phenobarbitone given alone. Following antipyrine 1200 mg with rifampicin 600 mg for 14 days a significantly greater increase in antipyrine clearance and 6-β-hydroxycortisol excretion was observed than when either drug was given alone.
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Breckenridge AM (1975) Clinical implications of enzyme induction. In: Park DV (ed) Enzyme induction. Plenum Press, London, pp 273–301
Breckenridge AM, Orme ML'E, Thorgeirsson SS, Davies DS, Brooks RK (1971) Drug interactions with warfarin: Studies with dichloralphenazone, chloral hydrate and phenazone (antipyrine). Clin Sci 40: 351–364
Brodie BB, Axelrod J, Soberman R, Levy BB (1949) The estimation of antipyrine in biological materials. J Biol Chem 179: 25–29
Danhof M, Krom DP, Breimer DD (1979) Studies on the different metabolic pathways of antipyrine in rats: influence of pheno barbital and 3-methyl-cholanthrene treatment. Xenobiotica 9: 695–702
Ohnhaus EE, Martin J, Kinser J, Colombo JP (1977) Enzyme induction and renal function in man. Br J Clin Pharmacol 4: 33–37
Ohnhaus EE, Park BK (1979) Measurement of urinary 6-β-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 15: 139–145.
Orme ML'E, Davies L, Breckenridge AM (1974) Increased glucuronidation of bilirubin in man and rat by administration of antipyrine (phenazone). Clin Sci Mol Med 46: 511–518
Miguet JP, Mavier P, Soussy CJ, Dhumeaux D (1977) Induction of hepatic microsomal enzymes after brief administration of rifampicin in man. Gastroenterology 72: 924–926
Park BK (1978) A specific radioimmunoassay for 6-β-hydroxycortisol in human. J Steroid Biochem 9: 963–966
Prescott LF (1969) Pharmacokinetic drug interactions. Lancet 2: 1239–1243
Sachs L (1978) Statistische Auswertungsmethoden. Springer, Berlin Heidelberg New York
Sanghvi A, Wight C, Parikh B, Desai H (1973) Urinary 17-hydroxycorticosteroid determination with p-hydrazinobenzene-sulfonic-acid-phosphoric-acid. Am J Clin Pathol 60: 684–690
Szasz G (1969) A kinetic photometric method for serum-γ-glutamyl-transpeptidase. Clin Chem 15: 124–136
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
Tredger JM, Smith HM, Powell-Jackson PR, Davis M, Williams R (1981) Effect of rifampicin on the mouse hepatic mixed-function oxidase system. Biochem Pharmacol 30: 1043–1051
Vesell ES (1979) The antipyrine test in clinical pharmacology: Conceptions and misconceptions. Clin Pharmacol Ther 26: 275–286
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Ohnhaus, E.E., Gerber-Taras, E. & Park, B.K. Enzyme-inducing drug combinations and their effects on liver microsomal enzyme activity in man. Eur J Clin Pharmacol 24, 247–250 (1983). https://doi.org/10.1007/BF00613826
- drug combinations
- enzyme induction
- antipyrine clearance