Effects of Oral Prasterone (Dehydroepiandrosterone) on Single-Dose Pharmacokinetics of Oral Prednisone and Cortisol Suppression in Normal Women

• Published in: Journal of clinical pharmacology 2001-11, Vol.41 (11), p.1195-1205
• Main Authors: Meno-Tetang, GuyM. L., Blum, Robert A., Schwartz, Kenneth E., Jusko, William J.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - blood; Adjuvants, Immunologic - pharmacokinetics; Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - therapeutic use; Administration, Oral; Adrenocorticotropic Hormone - administration & dosage; Adult; Algorithms; Area Under Curve; Biological and medical sciences; Circadian Rhythm; Cosyntropin - administration & dosage; Dehydroepiandrosterone - blood; Dehydroepiandrosterone - pharmacokinetics; Dehydroepiandrosterone - pharmacology; Dehydroepiandrosterone - therapeutic use; Dehydroepiandrosterone Sulfate - blood; Dehydroepiandrosterone Sulfate - pharmacokinetics; Drug Interactions; Female; Glucocorticoids - metabolism; Glucocorticoids - pharmacokinetics; Gonadal Steroid Hormones - blood; Gonadal Steroid Hormones - metabolism; Hormones. Endocrine system; Humans; Hydrocortisone - blood; Hydrocortisone - metabolism; Hydrocortisone - urine; Medical sciences; Models, Biological; Pharmacology. Drug treatments; Prednisolone - blood; Prednisone - metabolism; Prednisone - pharmacokinetics
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700122012742

This study sought to determine effects of multiple dosing of prasterone (DHEA, dehydroepiandrosterone) on the pharmacokinetics of prednisolone and endogenous 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 after200 mg/day of oral prasterone for one menstrual cycle (approximately 28 days). Identical assessments, timed to onset of menses, were conducted pretreatment (baseline) and at days 28 and 29 of prasterone treatment and included 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 assessed by Cmax, t1/2, 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 prasterone 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/day of prasterone did not alter either prednisolone pharmacokinetics or inhibition of cortisol secretion by prednisolone.