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Biochemical pharmacology

Biochemical pharmacology

IF: 5.3
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CYP3A mediates drug-drug interactions between atorvastatin and omeprazole: Evidence from in vitro and in vivo studies

Published:15 August 2025 DOI: 10.1016/j.bcp.2025.117241 PMID: 40819797
Chenmeizi Liang , Na Lu , Bingyi Yao , Yuanjin Zhang , Junze Huang , Yujia Yang , Yifei Shen , Xin Wang

Abstract

The simultaneous use of statins and proton pump inhibitors is common in clinical practice, but the mechanisms behind their potential drug-drug interactions (DDIs) are still not fully understood. This study investigates the cytochrome P450 3A (CYP3A)-mediated interactions between atorvastatin and omeprazole through in vitro microsomal assays and in vivo pharmacokinetic studies in wild-type (WT) and Cyp3a1/2 knockout (KO) rats. Incubation experiments with rat and human liver microsomes demonstrated that omeprazole inhibited atorvastatin metabolism in a concentration-dependent manner. In animal studies, WT and Cyp3a1/2 KO rats received either atorvastatin alone or with omeprazole, and the pharmacokinetics of atorvastatin were analyzed and compared across groups. The results showed that omeprazole significantly increased the maximum concentration and systemic exposure of atorvastatin in WT rats. Conversely, these DDIs were not observed in Cyp3a1/2 KO rats, indicating that CYP3A mediates these pharmacokinetic interactions. Therefore, it is important to monitor atorvastatin plasma concentrations closely in clinical settings and consider dose adjustments for patients taking omeprazole. This study offers valuable mechanistic insights into the interactions between atorvastatin and omeprazole, bridging preclinical findings with their therapeutic relevance.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
2-Hydroxy Atorvastatin Calcium Salt 265989-46-6 C33H37CaFN2O6 82 suppliers $135.00-$6123.00
2-Hydroxy Atorvastatin Calcium Salt 265989-46-6 C33H37CaFN2O6 82 suppliers $135.00-$6123.00
2-Hydroxy Atorvastatin Calcium Salt 265989-46-6 C33H37CaFN2O6 82 suppliers $135.00-$6123.00
2-Hydroxy Atorvastatin Calcium Salt 265989-46-6 C33H37CaFN2O6 82 suppliers $135.00-$6123.00
ORTHO-HYDROXY ATORVASTATIN 265989-46-6 - Inquiry
ORTHO-HYDROXY ATORVASTATIN 265989-46-6 - Inquiry

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