LC-MS/MS-based investigation of pharmacokinetic interactions between CYP3A4 substrates enzalutamide and repaglinide in rats

Polypharmacy is a common phenomenon in older patients with comorbidities. Prostate cancer patients often have diabetes complications, making them prone to administering multiple medications. Here, we explored the pharmacokinetic interactions between Enzalutamide (ENZ), prescribed for treating metastatic castration-resistant prostate cancer, and repaglinide (REP), used for type-2 diabetes. A novel, simple, and sensitive LC-MS/MS bioanalytical method was developed to simultaneously estimate ENZ and REP in rat plasma, aiding pharmacokinetic drug-drug interaction evaluation. Co-administration of these drugs in rats allowed assessment of the potential DDI. We report that ENZ, as a CYP3A4 inducer, alters the REP pharmacokinetic parameters, and clinicians must consider this before prescribing them.