Investigation of the Inhibitory Effect of Simvastatin on the Metabolism of Lidocaine Both in vitro and in vivo.

Background: Lidocaine has cardiovascular and neurologic toxicity, which is dose-dependent. Due to CYP3A4-involved metabolism, lidocaine may be prone to drug-drug interactions.

Materials And Methods: Given statins have the possibility of combination with lidocaine in the clinic, we established in vitro models to assess the effect of statins on the metabolism of lidocaine.

Functional characterization of 27 CYP3A4 variants on macitentan metabolism in vitro.

Objective: Macitentan is a new choice for pulmonary hypertension treatment which is converted to active metabolite ACT132577 by human cytochrome P450 3A4. Human cytochrome P450 3A4 often occurred gene mutations. Gene polymorphism might cause a variety of changes of protein expression and thus give rise to metabolic difference.

Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS.

The epidemic of loperamide abuse and misuse in the patients for the alternative to opioids has become an increasing worldwide concern and has led to considerations about the potential for drug-drug interactions between loperamide and other combined drugs, especially inhibitors of cytochrome P450 (CYP450) enzymes, such as axitinib. This study assessed the effects of axitinib on the metabolism of loperamide and its main metabolite N-demethylated loperamide in rats and in rat liver microsomes (RLM), human liver microsomes (HLM) and recombinant human CYP3A4*1. The concentrations of both compounds were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Functional characterization of 27 CYP3A4 protein variants to metabolize regorafenib in vitro.

Aim: Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we had discovered several novel CYP3A4 variants.