Feet of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats.
| Title in English | Effect of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats. |
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| Authors | |
| Year of publication | 2005 |
| Type | Article in Periodical |
| Magazine / Source | Eur J Drug Metab Pharmacokinet |
| MU Faculty or unit | |
| 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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