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Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion
Author(s) -
Glynn Anne M,
Slaughter Richard L,
Brass Corstiaan,
D'Ambrosio Robin,
Jusko William J
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.114
Subject(s) - ketoconazole , methylprednisolone , pharmacokinetics , corticosteroid , medicine , pharmacology , endocrinology , volume of distribution , antifungal , dermatology
The disposition of methylprednisolone was examined in six normal subjects after the injection of 20 mg iv methylprednisolone sodium succinate. Disposition studies were performed both without and with ketoconazole, 200 mg/day, for 6 days. Ketoconazole increased the methylprednisolone AUC and mean residence time (by 135% and 66%, respectively) and decreased clearance (60%), the terminal phase slope, and the volume of distribution. These findings are typical of macrolide antibiotic alteration of methylprednisolone disposition and consistent with reports of inhibition of drug metabolism by ketoconazole. Methylprednisolone reduced the 24‐hour cortisol AUC by 44%, but morning cortisol concentrations returned to normal. Ketoconazole with methylprednisolone further reduced the 24‐hour cortisol AUC and suppressed morning cortisol concentrations. Thus ketoconazole inhibits methylprednisolone disposition and extends the adrenal suppression effects of this corticosteroid. Clinical Pharmacology and Therapeutics (1986) 39, 654–659; doi: 10.1038/clpt.1986.114