The Novel Atypical Antipsychotic Lurasidone Affects Cytochrome P450 Expression in the Liver and Peripheral Blood Lymphocytes

Lurasidone is a novel atypical antipsychotic drug acting on dopaminergic, serotonergic and noradrenergic receptors; it is applied for the long-term treatment of schizophrenia and depression in patients with bipolar disorders. We aimed at performing a comparative study on the influence of chronic treatment with lurasidone on the expression of cytochrome P450 enzymes in the liver and in peripheral blood lymphocytes, and to evaluate the relationship between changes in the expression of CYP enzymes in the two experimental models. The obtained results show a fairly similar expression pattern of the main CYP enzymes in the rat livers and lymphocytes, and they indicate that in the liver, lurasidone exerts an inhibitory effect on the activity, protein and mRNA levels of CYP2B1/2 (not CYP2B2 mRNA), CYP2C11 and CYP2E1, while in the case of CYP3A1 and CYP3A2, it causes enzyme induction. At the same time, lurasidone decreases the expression of CYP2B, CYP2C11 (CYP2C11 protein only) and CYP2E1 but increases that of CYP3A2 (not CYP3A1) in lymphocyte cells. In conclusion, chronic treatment with lurasidone simultaneously and in the same way influences the expression and activity of CYP2B, CYP2C11, CYP2E1 and CYP3A2 in the liver and peripheral blood lymphocytes of rats. Thus, the lymphocyte cytochrome P450 profile may be utilized as an indicator of the hepatic cytochrome P450 profile in further clinical studies with lurasidone, and lymphocytes may serve as easily available surrogates for examining the impact of new drugs and chronic in vivo treatments on CYP enzyme expression, as well as to estimate drug-drug interactions and toxicity risk.

Automated summary

This study compares the effects of chronic treatment with Lurasidone on the expression of cytochrome P450 enzymes in rat liver and peripheral blood lymphocytes. It was found that Lurasidone inhibits the activity, protein and mRNA levels of CYP2B1/2, CYP2C11, and CYP2E1 in the liver, while inducing CYP3A1 and CYP3A2. In lymphocytes, Lurasidone decreases the expression of CYP2B, CYP2C11 (protein only), and CYP2E1, but increases CYP3A2 expression. These findings suggest that lymphocyte cytochrome P450 profile can be used as an indicator of hepatic cytochrome P450 profile in further clinical studies.