Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate.

The Journal of Clinical Endocrinology and Metabolism
M R Stjernholm, F H Katz

Abstract

The metabolic clearance rates (MCR) of methylprednisolone (MP) (no. = 13) and methylprednisolone-21- Na-hemisuccinate (MPHS) (no. = 6) were studied in normal humans using tritium-labeled steroids. The cumulative appearance of the labeled steroid was examined for the whole urine and for three major urinary fractions. The MCR, half-life, and volume of distribution were, respectively, 383 +/- 72 (SD) liters/day, 165 +/- 49 minutes, and 61 +/- 12 liters for MP, and 234 +/- 37, 160 +/- 19, and 41 +/- 6 for MPHS. Diphenylhydantoin (DPH) administered to 4 subjects increased the MCR of MP from 424 +/- 71 to 977 +/- 132 (P less than 0.01), and decreased the half-life from 149 +/- 44 to 69 +/- 7 (P less than 0.001). Similar effects were found with phenobarbital (PB). Diazepam (DZP) had no effect. Major increases in urinary metabolites after DPH and PB were in the unconjugated ethyl acetate fraction, and this suggests that MP metabolism is significantly altered by hepatic microsomal hydroxylation enzyme induction by DHP and PB, but not DZP. This could occur with the formation of a 6beta-hydroxy derivative which could be readily cleared by the kidney. The urinary pattern of excretion for MPHS was similar to that of MP. The MCR of MPHS was ...Continue Reading

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