Journal
JOURNAL OF CLINICAL PHARMACOLOGY
Volume 47, Issue 12, Pages 1532-1539Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0091270007308617
Keywords
budesonide; cortisol; CYP3A; metronidazole
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Recent case reports suggest that addition of high-dose metronidozole might be associated with elevated plasma concentrations of substrates of cytochrome P450 (CYP) 3A. Because patients with fistulizing Crohn's disease benefit by using high doses of metronidazole for prolonged periods, this study's primary aim was to evaluate the effect of high-dose metronidazole on the pharmacokinetics of oral budesonide, a sensitive substrate of GYP3A commonly prescribed in acute inflammatory bowel disease. Twelve healthy adults received 1.5 g metronidazole per day over 1 week. The CYP3A-dependent metabolic profile of an oral dose of budesonide (3 mg) and that of endogenous cortisol were compared intraindividually before and after administration of metronidazole. There was neither a significant effect of high-dose metronidazole on the area under the plasma concentration-time curve (AUG) of budesonide (90% confidence interval, 79%-115%) nor on the AUC ratios of 6 beta-hydroxybudesonide/budesonide and 16 alpha hydroxyprednisolone/budesonide. In parallel, metronidazole did not significantly alter formation of 6 beta-hydroxycortisol. Vice versa, budesonide did not affect the AUC of metronidazole (90% confidence interval, 91%-100%). The authors conclude that in contrast to concomitant intake of other imidazoles such as ketoconazole, concomitant intake of metronidazole may not lead to serious safety concerns due to elevated systemic concentrations of the glucocorticoid budesonide.
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