Abstract
Dostalek M., J. Pistovaakova, V. Minafiikova, J. Jufiica, J T omandl, E. Hada‰ova: Effect of Acute and Repeated Administration of Methamphetamine on the Activity of CYP2D in Isolated Perfused Rat Liver. Acta Vet. Brno 2005, 74: 339-345. The aim of this study was to ascertain the influence of acute and repeated methamphetamine administration on metabolic activity of CYP2D2. The study was performed in the model of isolated perfused rat liver using dextromethorphan as a specific marker of CYP2D2 activity. Acute administration of methamphetamine (10, 20 or 40 mg/kg, i.p., once daily for two days) significantly increased dextrorphan O-formation in the isolated liver mediated by CYP2D2 at all investigated doses in the 120th min of liver perfusion. Repeated administration of methamphetamine (10, 20 or 40 mg/kg, i.p., once daily for six days) significantly stimulated dextromethorphan Odemethylation via CYP2D2 dose-dependently. Thus, an induction of CYP2D2 metabolic activity was proved in these experiments. With regard to a high level of homology between human and rat CYP isoform studied, the results may have clinical impact in pharmacotherapy of methamphetamine abusers. Methamphetamine, Dextromethorphan, CYP2D, liver, isolated perfused, rat
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