Abstract: AIM: To identify the isoforms of cyto-chrome P450 (CYP) involved in the metabolism of mir-tazapine and the influence of mirtazapine on the me-tabolism of mirtazapine. METHODS: Mirtazapine was incubated with rats liver microsomes induced by different inducers, and the reaction was terminated by acetonitrile. The sample was added 25%ammonia water and extracted with cyclohexane, and the determination was performed by RP-HPLC with the mobile phase of methanol-water (including 10 mmol°L^-1 NH 4 AC, 5 mmol°L^-1 SDS, pH 3.5) 62 :38(V/V). RESULTS: The assay was linear from 75.3 to 565 μmol°L^-1 for mirtazapine in rat hepatic microsomal incubates.The livers induced by phenobarbi-tal were catalyzed and livers induced by rifampicin also showed more active performance, while the livers induced by rats had no significant difference between two groups. CONCLUSION: P450 3A4 induced by phenobarbital as well as rifampicin is crucial in the metabolism of mirtaza-pine. And P450 2C9/2C19 induced by rifampicin may al-so interfere the metabolism of mirtazapine. Mirtazapine has no obvious effect on the isoforms responsible for its metabolism of mirtazapine.

Key words: KEY WOEDS mirtazapine, HPLC, liver microsomes, in vitro metabolism