Feet of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats.

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Title in English Effect of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats.
Authors

DOSTÁLEK Miroslav HADAŠOVÁ Eva HANESOVÁ Mariana PISTOVČÁKOVÁ Jana ŠULCOVÁ Alexandra JUŘICA Jan TOMANDL Josef LINHART Igor

Year of publication 2005
Type Article in Periodical
Magazine / Source Eur J Drug Metab Pharmacokinet
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords Midazolam; Methamphetamine; Cytochrome P-450; CYP3A1/2 isozyme
Description Methamphetamine is the fourth most frequently cited drug of abuse on treatment centre admission records behind cocaine, heroin and marijuana. We investigated the effect of methamphetamine (10 mg/kg, i.p., once daily for six days) on the pharmacokinetics of midazolam a substrate for rat cytochrome P-450 3A. Animals received a single injection of midazolam (5 mg/kg) in tail vein 24 h after the last dose of methamphetamine and placebo. Validated HPLC method was used to quantify all compounds of interest. The elimination half-life (t1/2) and the area under the concentration-time curve of midazolam were significantly reduced by pretreatment with methamphetamine to 63.8 % and 66.3 of control value, respectively and the clearance of midazolam was significantly increased by methamphetamine pretreatment. The results showed that administration of methamphetamine significantly stimulated metabolic activity of CYP3A1/2. With regard to a high level of homology between human and rat CYP isoforms studied, the results may have clinical impact in pharmacotherapy of methamphetamine abusers.
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