Comparison of Pharmacokinetics and Bioavailability of Fixed‐Dose Combination Tablet and Monotherapy Combination of Allisartan Isoproxil and Indapamide Sustained‐Release in Healthy Chinese Volunteers

Abstract

AbstractThis study aimed to compare the pharmacokinetics and bioavailability of 2 formulations: a fixed‐dose combination tablet containing allisartan isoproxil (AI) and indapamide sustained‐release (SR), and a monotherapy combination of AI and indapamide SR, in healthy Chinese subjects. A monocentric, open‐label, single‐dose, randomized, 2‐way crossover study design was implemented. A total of 38 healthy male and female volunteers were equally divided into 2 treatment sequences. The analysis of plasma concentrations was conducted using a nonstereospecific liquid chromatography/tandem mass spectrometric method. The primary pharmacokinetic parameters were calculated using a noncompartmental model. Safety assessments were performed throughout the study. For the fixed‐dose combination and monotherapy combination, the mean values of EXP3174 (metabolite of AI) Cmax, AUC0‒t, and AUC0‐∞ were 987 and 999 ng/mL, 8059 and 7749 ng/mL h, and 8332 and 8007 ng/mL h, respectively. The corresponding values for indapamide were 27 and 32 ng/mL, 1002 and 1105 ng/mL h, and 1080 and 1172 ng/mL h. No serious adverse events were reported during the study. The combination tablet containing 240 mg of AI and 1.5 mg of indapamide SR met the bioequivalence standards. Additionally, both formulations were tolerated and had good safety profiles in the research.