METHAMPHETAMINE-INDUCED CHANGES IN DEXTROMETHORPHAN AND MIDAZOLAM METABOLISM IN RATS: A PHARMACOKINETIC STUDY
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Proceedings |
| Conference | 19th European Workshop on Drug Metabolism. Abstract & Program Book. |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | drug metabolism; methamphetamine; dextromethorphan; midazolam; CYP2D6; CYP3A4; pharmacokinetics; |
| Description | Methamphetamine (pervitine) is one of the most frequently abused substances. The drug is metabolized by the hepatic cytochromes P450, mainly by CYP2D and CYP3A. The present pharmacokinetic study in the rat investigated the possible influence of methamphetamine on metabolic fates of model substrates for CYP3A1/2 and CYP2D1/2. The pharmacokinetic analysis showed a marked stimulatory effect of methamphetamine on CYP2D1/2, as it was previously demonstrated by us in the isolated perfused rat liver. Similarly, the midazolam kinetics (marker of CYP3A1/2 activity) showed a significantly increased CYP3A-mediated metabolism. The results may have clinical impact in pharmacotherapy of methamphetamine abusers. |
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