Effects of oral prasterone (dehydroepiandrosterone) on single-dose pharmacokinetics of oral prednisone and cortisol suppression in normal women

This study sought to determine effects of multiple dosing of prosterone (DH EA, dehydroepiandrosterone) on the pharmacokinetics of prednisolone and end ogenous cortisol secretion. These drugs are likely to be coadministered to patients with systemic lupus erythematosus. Fourteen normal women (ages 30. 1 +/- 5.4 years) received single-dose oral prednisone (20 mg) before and af ter 200 mg/day of oral prasterone for one menstrual cycle (approximately 28 days). Identical assessments, timed to onset of menses, were conducted pre treatment (baseline) and at days 28 and 29 of prasterone treatment and incl uded serum total and free prednisolone, prednisone, DHEA, DHEA-S (dehydro- epiandrosterone sulfate), ACTH-stimulated cortisol, and sex hormones and 24 -hour urine free cortisol. Pharmacokinetic parameters of prednisolone as as sessed by C-max, t(1/2), AUC, or serum protein binding were not affected by prasterone. The ACTH-stimulated plasma cortisol concentrations were mildly reduced, but 24-hour urine free cortisol excretion was unchanged during pr asterone administration. Serum androstenedione and testosterone increased, while no changes in serum estradiol or estrone occurred. The administration of 200 mg oral prasterone produced serum concentrations of DHEA and DHEA-S significantly greater than endogenous levels. Chronic dosing with 200 mg/d ay of prasterone did not alter either prednisolone pharmacokinetics or inhi bition of cortisol secretion by prednisolone.