Pharmacokinetic and bioequivalence of two formulations of Valsartan/Amlodipine Tablet(I) in healthy Chinese volunteers: A randomized, three-period, partially replicated crossover study

Valsartan/amlodipine combination tablets can exert synergistic antihypertensive effects through different mechanisms, significantly lowering blood pressure while also addressing multiple risk factors and comorbidities in patients. This study designed a single-center, randomized, open-label, two-formulations, single-dose, three-cycle, three-sequence, partially repeated crossover controlled trial design. A total of 72 healthy Chinese volunteers participated in the fasting and fed trials, of whom 69 completed the trial process. This study employed a methodologically validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentrations of valsartan and amlodipine in plasma. Phoenix WinNonlin software (version 7.0) was used to calculate pharmacokinetic parameters using a non-compartmental model. Equivalence analysis was performed using the average bioequivalence (ABE) method and the reference-scaled average bioequivalence (RSABE) method. The trial results showed that the test drug was bioequivalent to the reference drug, and no suspected serious adverse reactions or serious adverse events occurred throughout the trial. The results of this study support the launch of the new generic Valsartan/Amlodipine Tablet(I) in China. As a representative antihypertensive fixed-dose combination (FDC), these methodological insights can be directly applied to clinical trials of similar drug products, thereby enhancing success rates while mitigating development risks.Clinical trial registration: CTR20221889, ( http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml.28/07/2022 ).