Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.
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Shord SS, Chan LN, Camp JR, Vasquez EM, Jeong HY, Molokie RE, Baum CL, Xie H
Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.
Br J Clin Pharmacol. 2010 Feb;69(2):160-6. doi: 10.1111/j.1365-2125.2009.03559.x.
- PubMed ID
- 20233179 [ View in PubMed]
- Abstract
AIMS: The aim of the study was to determine the effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam in the plasma. METHODS: We conducted a randomized, open-label, four-way crossover study in 10 healthy volunteers. Each volunteer received oral midazolam 2 mg or intravenous midazolam 0.025 mg kg(-1) with and without oral clotrimazole troches 10 mg taken three times daily for 5 days. Each study period was separated by 14 days. Serial blood samples were collected up to 24 h after oral midazolam and 6 h after intravenous midazolam. Plasma concentrations for midazolam and its metabolite 1-hydroxymidazolam were measured and fitted to a noncompartmental model to estimate the pharmacokinetic parameters. RESULTS: Ten healthy volunteers aged 21-26 years provided written informed consent and were enrolled into the study. Clotrimazole decreased the apparent oral clearance of midazolam from 57 +/- 13 l h(-1)[95% confidence interval 48, 66] to 36 +/- 9.8 l h(-1) (95% confidence interval 29, 43) (P= 0.003). These changes were accompanied by a decrease in the area under the concentration-time curve (mean difference 22 microg h(-1) l(-1), P= 0.001) and bioavailability (mean difference 0.21, P= NS). There were no significant differences in the systemic clearance of midazolam with or without clotrimazole troches. CONCLUSIONS: Oral clotrimazole troches decreased the apparent oral clearance of midazolam; no significant differences in the systemic clearance of midazolam were found.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Clotrimazole Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails