MEASUREMENT OF URINARY 6-BETA-HYDROXYCORTISOL EXCRETION AS AN INVIVO PARAMETER IN THE CLINICAL-ASSESSMENT OF THE MICROSOMAL ENZYME-INDUCING CAPACITY OF ANTIPYRINE, PHENOBARBITONE AND RIFAMPICIN

To assess the rate of drug metabolism in man, four different in vivo measurements of microsomal enzyme activity were compared before and after the administration of three drugs known to be enzyme inducers in man: antipyrine, phenobarbitone and rifampicin. 27 healthy volunteers, divided into four different groups, were given antipyrine 1000 mg or 1200 mg, phenobarbitone 100 mg and rifampicin 600 mg or 1200 mg daily for 14 days. Before and after each drug, estimates were made of total body clearance of antipyrine, γ-glutamyl-transpeptidase in plasma and d-glucaric acid, 6-β-hydroxycortisol and 17-hydroxycorticosteroid urinary excretion in 24 h, as parameters of hepatic microsomal enzyme activity. Following treatment with antipyrine, phenobarbitone or rifampicin 600 mg daily, the total body clearance of antipyrine increased by 44-60%, and after rifampicin 1200 mg there was an increase up to 125%. d-Glucaric acid excretion in urine showed a tendency to increase to the same extent in every group investigated, and γ-glutamyl-transpeptidase increased similarly following antipyrine and phenobarbitone, although it remained unchanged following rifampicin administration. Urinary excretion of 6-β-hydroxycortisol, corrected by the 17-hydroxycorticosteroids representing the percentage proportion of 6-β-hydroxycortisol of the total amount of 17-hydroxycorticosteroids excreted, increased from 4.6-5.2% up to 9.5-28.3% depending upon the drug given. Comparing all in vivo parameters of hepatic microsomal enzyme activity by means of linear regression, a significant correlation was found between total body clearance of antipyrine and urinary excretion of 6-β-hydroxycortisol, while none of the other parameters showed any significant correlation. In addition, a better seperation of the enzyme-inducing capacity of different drugs was seen using 6-β-hydroxycortisol as a parameter of microsomal enzyme activity. Therefore, measurement of 6-β-hydroxycortisol corrected by the 17-hydroxycorticosteroid excretion, combined with estimation of the total body clearance of antipyrine, gives a valuable index, suitable for use in further studies of induction in man. © 1979 Springer-Verlag.