Bioequivalence of bosentan tablets in healthy Chinese volunteers

doi:10.12092/j.issn.1009-2501.2019.06.012

Abstract

Abstract:

AIM: To evaluate the bioequivalence of a single oral dose of bosentan tablets of test and reference formulations in healthy Chinese volunteers. METHODS: It was a randomized, open-label, two sequences, two period crossover study. A single oral dose of 125 mg test and reference formulations were given to 24 healthy Chinese volunteers under fasting and fed conditions. The concentrations of bosentan and its active metabolite hydroxybosentan in plasma were determined by high performance liquid chromatography tandem mass spectrometry. The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of WinNonlin program. RESULTS:The bosentan's major pharmacokinetic parameters of test and reference under fasting condition were as follow: Cmax were (2.72±1.09) and (2.59±1.02) μg/mL, AUC0-t were (13.51±4.55) and (12.61±4.25) μg·mL-1·h, AUC0-∞ were (14.04±4.46) and (13.02±4.24) μg·mL-1·h, tmax were (3.75±0.81) and (3.98±0.76) h, t1/2 were (2.70±0.88) and (2.77±0.91) h。The bosentan's major pharmacokinetic parameters of test and reference under fed condition were as follow: Cmax were (2.84±0.68) and (2.95±0.99) μg/mL, AUC0-t were (14.66±4.27) and (15.34±6.09) μg·mL-1·h, AUC0-∞ were (15.04±4.41) and (15.68±6.19) μg·mL-1·h, tmax were (3.98±1.05) and (3.98±1.21) h, t1/2 were (2.55±0.65) and (2.71±0.63) h. There was no significant difference among the order of administration, formulations and cycles (P>0.05); The 90% confidence intervals of AUC0-t, AUC0-∞ and Cmax were in the range of 80%-125% by double-sided t test at the level of α=0.05.CONCLUSION: The two formulations of bosentan tablets were bioequivalent in Chinese healthy volunteers under fasting and fed condition.

Key words: bosentan tablets, bioequivalence, HPLC-MS/MS

CLC Number:

R969.1

XU Yichao, LOU Honggang, RUAN Zourong, CHEN Jinliang, JIANG Bo, SHAO Rong, YANG Dandan. Bioequivalence of bosentan tablets in healthy Chinese volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(6): 675-680.

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