Premium
Bioequivalence Study of 2 Formulations of Rivaroxaban, a Narrow‐Therapeutic‐Index Drug, in Healthy Chinese Subjects Under Fasting and Fed Conditions
Author(s) -
Ding Sijia,
Wang Lu,
Xie Lijun,
Zhou Sufeng,
Chen Juan,
Zhao Yuqing,
Deng Wenjie,
Liu Yun,
Zhang Hongwen,
Shao Feng
Publication year - 2020
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.742
Subject(s) - bioequivalence , pharmacokinetics , medicine , rivaroxaban , crossover study , geometric mean , area under the curve , pharmacology , chromatography , chemistry , mathematics , statistics , alternative medicine , pathology , warfarin , placebo , atrial fibrillation
This study aimed to evaluate the bioequivalence (BE) of 2 formulations of the 10‐mg rivaroxaban tablet. The study was a randomized, open‐label, 4‐period, crossover study that included 28 healthy subjects in fasting or fed conditions. The pharmacokinetic parameters were determined based on the concentrations of rivaroxaban using high‐performance liquid chromatography with a tandem mass spectrometer detector. In each of the 4 study periods with fasting or fed conditions, a single dose of test or reference product was administered. Rivaroxaban concentrations in plasma were determined using a validated liquid chromatography with a tandem mass spectrometer detector method. The pharmacokinetic parameters assessed were the area under the plasma concentration‐time curve (AUC 0‐t , AUC 0‐∞ ), the peak plasma concentration of the drug (C max ), time to achieve C max , elimination half‐life, within‐subject variability of test drug, and within‐subject variability of reference drug. The geometric mean ratio (90%CI) of the test drug/reference drug for rivaroxaban was 90.38% to 103.60% for AUC 0‐t in fasting conditions and 90.13% to 100.42% in fed conditions. The AUC 0‐∞ s were 89.94% to 102.50% and 90.14% to 100.45% under fasting and fed conditions, respectively. The C max values were 90.58% to 105.01% and 96.36% to 108.07% in these 2 conditions, respectively. All 90%CIs for test drug/reference drug geometric mean ratio were ≤2.5. The 90%CIs for test/reference AUC ratio and C max ratio were within the acceptable range for BE. There were no adverse events encountered during this BE study. The study's results indicated that the 2 formulations of the rivaroxaban tablet were bioequivalent.