Effects of anti-hypertensive drugs on the metabolism of mobocertinib in rats both in vitro and in vivo

This study investigates the potential drug-drug interactions between commonly prescribed anti-hypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. The study used UPLC-MS/MS to detect the essential metabolites of mobocertinib in rat liver microsomes. Moreover, several anti-hypertensive drugs were used as inhibitors and the IC 50 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 ( SD) rats were randomly divided into five 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 five groups and then blood samples were collected for further analysis. UPLC-MS/MS was performed to analyze the concentration of mobocertinib and its metabolites in rat plasma. Most anti-hypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. Several anti-hypertensive 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 anti-hypertensive drugs interact with mobocertinib and additional attention is needed when co-administering the two drugs.