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Impact of ketoconazole on the metabolism of prednisolone
Author(s) -
Zürcher Regula M,
Frey B M,
Frey F J
Publication year - 1989
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.1989.42
Subject(s) - ketoconazole , prednisolone , pharmacology , metabolism , medicine , dermatology , antifungal
The impact of ketoconazole (200 mg for 7 days) on the kinetics of oral prednisone and intravenous prednisolone and on the apparent activity of the 6 β‐hydroxylase was investigated in 10 healthy volunteers. The ratio of urinary 6β‐OH‐cortisol/17‐OH‐corticosteroids declined by >50% and the urinary excretion of 6β‐OH‐prednisolone decreased more than twofold in all subjects. The decline of the activity of the 6β‐hydroxylase was associated with impaired metabolic and renal clearances of total and unbound prednisolone. The ratios of the AUCs of prednisolone/prednisone after oral prednisone and intravenous prednisolone were independent of the administration of ketoconazole, suggesting that the enzymes responsible for the interconversion of prednisolone ⇄ prednisone were not affected by ketoconazole. Thus ketoconazole inhibits 6β‐hydroxylase and increases the exposure of the body to the biologically active unbound prednisolone after oral prednisone or intravenous prednisolone. Clinical Pharmacology and Therapeutics (1989) 45, 366–372; doi: 10.1038/clpt.1989.42