ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1567044
Evaluation the inhibitory effect of nicardipine on the metabolism of quetiapine
Provisionally accepted
- 1The Third Clinical Institute Affiliated to Wenzhou Medical University (Wenzhou People’s Hospital), wenzhou, China
- 2First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 3Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China
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The aim of this study was to investigate the impact of calcium channel blockers (CCBs) and antihypertensive traditional Chinese medicine (TCM) on the metabolism of quetiapine. In vitro, two incubation systems of rat liver microsomes (RLM) and human liver microsomes (HLM) were established and optimized to explore potential interactions between 5 kinds CCBs (nicardipine, dilthiazem, lercanidipine, nimodipine, nitrendipine), 5 kinds antihypertensive TCM (quercetin, fangchinoline, apigenin, tetrandrine, and berberine) and quetiapine, and to evaluate their underlying inhibition mechanisms. In vivo, Sprague-Dawley rats were used to assess the interaction between quetiapine and nicardipine. The results showed that nicardipine had the highest inhibition rate (79.22%) against quetiapine metabolism among those drugs screened. The half-maximal inhibitory concentration (IC50) values for the inhibition of quetiapine metabolism by nicardipine in RLM and HLM were similar, at 10.29 ± 0.06 μM and 13.23 ± 0.37 μM, respectively. In RLM, nicardipine exhibited a mixed mechanism of competitive and non-competitive inhibition, while in HLM, it displayed a non-competitive and un-competitive inhibition mechanism. In vivo results indicated that nicardipine could significantly increase the main pharmacokinetic parameters AUC(0-t), AUC(0-∞), and Cmax of quetiapine, but decrease the AUC(0-t) of its metabolite N-desalkylquetiapine. The findings of this study suggested that nicardipine had inhibited the metabolism of quetiapine, suggesting the dose adjustment or therapeutic drug monitoring of quetiapine should be conducted to achieve individualized therapy.
Keywords: quetiapine, Nicardipine, drug-drug interactions, UPLC-MS/MS, microsome
Received: 26 Jan 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 Yang, Xia, Li, Li, Cao and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hailun Xia, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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