URINARY 6-BETA-HYDROXYPREDNISOLONE EXCRETION INDICATES ENHANCED PREDNISOLONE CATABOLISM

  • 1 January 1983
    • journal article
    • research article
    • Vol. 101  (4) , 593-604
Abstract
Patients with enhanced catabolism of prednisolone exhibit a reduction in steroid efficacy. Since prednisolone never reaches steady state at the usual dosage, the clearance rate can only be estimated by determining the area under the plasma concentration-time curve after an i.v. dose of prednisolone. To obviate that time-consuming procedure for screening of patients with enhanced prednisolone metabolism, a quantitative assay was developed for 6.beta.-hydroxyprednisolone in urine to determine whether the urinary excretion of 6.beta.-hydroxyprednisolone increases concomitantly with the clearance rate of total and of unbound prednisolone in subjects with an enhanced catabolism of prednisolone. The results are given separately for males and females because there is some debate as to whether females compared to males exhibit a higher capacity of the liver to hydroxylate steroids at the 6th position. Before and during the administration of phenytoin the total body clearance of total and of unbound prednisolone and the urinary excretion of prednisolone and of 6.beta.-hydroxyprednisolone were determined in 6 female and 8 male volunteers. The fraction of the i.v. dose of prednisolone excreted in urine as 6.beta.-hydroxyprednisolone was higher in females than in males (P < 0.001) and increased during phenytoin dosing from 6.4-10.4% (range) to 15.6-20.4% in females and from 2.4-7.2% to 12.2-18.3% in males. The ratio of 6.beta.-hydroxyprednisolone to prednisolone in urine increased linearly with the nonrenal clearance of both total and unbound prednisolone. This is the 1st demonstration that the fractional excretion of 6.beta.-hydroxyprednisolone increased after the induction of the microsomal liver enzymes. Thus measurements of urinary 6.beta.-hydroxyprednisolone excretion may be of potential value to detect patients with enhanced catabolism of prednisolone.