Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.
Br J Clin Pharmacol
; 69(2): 160-6, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-20233179
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ansiolíticos
/
Midazolam
/
Clotrimazol
/
Citocromo P-450 CYP3A
/
Antifúngicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article