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Abstract
Amphetamine-based drugs, including methamphetamine, are some of the most widely used illegal drugs in the world. Methamphetamine is metabolized by the cytochrome P450s, the latter also being involved in the metabolism of many drugs and other xenobiotics. The effect of methamphetamine pretreatment (10 mg kg–1, intraperitoneally once daily for 6 days) on the activity of the P450 enzymes was assessed both in the rat isolated perfused liver and in vivo. The rate of 4-hydroxydiclofenac production was significantly enhanced in vivo, indicating a possible stimulatory effect on P4502C6. Similarly, the kinetics of tolbutamide and dextromethorphan in isolated perfused rat liver indicate a significant increase in both P4502C6 and the P4502D subfamily. No significant changes in midazolam kinetic in the isolated perfused rat liver were observed. The potential for methamphetamine to cause drug interactions is of clinical relevance and, therefore, it warrants further investigation. Until further drug interaction experiments are accomplished, the co-administration of drugs with methamphetamine should be conducted with caution.
Acknowledgement
This work was supported by the Czech Ministry of Education (Project Numbers CEZ: J07/98:141100001 and MSM 0021622404). The authors acknowledge Hoffmann-LaRoche in Basel, Switzerland, for the sample of midazolam; Janssen Pharmaceutica in Beerse, Belgium, for the sample of ketoconazole; and Merck in Prague, Czech Republic, for the sample of dexamethasone sodium salt. The authors also thank Jana Valova and Jana Adamkova for excellent technical assistance.