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Updated: Oct 28, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
The effect of repeated administration of lumateperone on cytochrome P450 expression and activity in rat liver
Przemysław J Danek1, Renata Pukło2, Władysława A Daniel2
1Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, 31-343, Poland. przemyslaw.danek@if-pan.edu.pl.
Background:
Antipsychotic drugs are used for long-term treatment of schizophrenia and other psychotic-related symptoms. Our present work aimed at investigating the effects of chronic administration of the third-generation antipsychotic drug lumateperone on the expression of cytochrome P450 (CYP) enzymes involved in drug metabolism and transcription factors in rat liver.
Methods:
Male Wistar rats received lumateperone (1 mg/kg) once daily for 14 days. 24 h after the last dose, their livers were excised, and CYP enzyme expression and activity were measured. In addition, the expression of transcription factors and serum hormone concentrations were evaluated.
Results:
Lumateperone significantly increased the CYP expression and/or activity of CYP2A, CYP2B, and CYP3A enzymes, but decreased that of CYP2D enzymes. The observed changes in CYP enzymes were in line with alterations in transcription factors: lumateperone elevated the mRNA level of PXR and reduced that of FXR in the liver. Simultaneously, increased corticosterone levels and decreased T4 levels in serum were observed.
Conclusion:
Repeated lumateperone administration modulated the expression and activity of selected hepatic CYP enzymes in rats. These findings indicate biological effects on hepatic drug-metabolizing pathways in a rat model. Relevance to human drug-drug interactions remains to be established in in vitro pharmacokinetic studies.
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