Dafa Yi, Jiazong Ye, Zebei Lu, Leilei Lu, Tengfei Qi, Tong Luo, Xiuyun Peng, Abdullah Al Mamun, Quan Zhou, Daqing Chen, Shuanghu Wang
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引用次数: 0
Abstract
This study investigates the potential drug-drug interactions between commonly prescribed antihypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. The study used ultra-performance liquid chromatography-mass spectrometry to detect the essential metabolites of mobocertinib in rat liver microsomes. Moreover, several antihypertensive drugs were used as inhibitors and the IC50 values were determined for calcium channel blockers, angiotensin II receptor blockers, and α and β receptor blockers against mobocertinib. The inhibitory mechanism of mobocertinib was further investigated for nicardipine, irbesartan, telmisartan, carvedilol, prazosin hydrochloride, and spironolactone. Twenty-five Sprague-Dawley rats were randomly divided into 5 groups: benidipine, nicardipine, telmisartan, irbesartan and blank control groups. The drugs were administered over a period of 7 days. Mobocertinib was administered once by gavage to 5 groups, and then blood samples were collected for further analysis. Ultra-performance liquid chromatography-mass spectrometry was performed to analyze the concentration of mobocertinib and its metabolites in rat plasma. Most antihypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. Several antihypertensive drugs were also found to increase the plasma concentration and decrease the metabolic rate of mobocertinib when administered multiple times. More importantly, we found that benidipine, nicardipine, telmisartan, and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo. In summary, our data reveal that antihypertensive drugs interact with mobocertinib and additional attention is needed when coadministering the 2 drugs. SIGNIFICANCE STATEMENT: This study investigates the potential drug-drug interactions between commonly prescribed antihypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. In this study, the most common antihypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. We found that benidipine, nicardipine, telmisartan, and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo.
期刊介绍：
An important reference for all pharmacology and toxicology departments, DMD is also a valuable resource for medicinal chemists involved in drug design and biochemists with an interest in drug metabolism, expression of drug metabolizing enzymes, and regulation of drug metabolizing enzyme gene expression. Articles provide experimental results from in vitro and in vivo systems that bring you significant and original information on metabolism and disposition of endogenous and exogenous compounds, including pharmacologic agents and environmental chemicals.
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