Bioequivalence Study of 2 Formulations of Rivaroxaban, a Narrow‐Therapeutic‐Index Drug, in Healthy Chinese Subjects Under Fasting and Fed Conditions. Issue 3 (14th October 2019)

• Record Type: Journal Article
• Authors: Ding, Sijia; Wang, Lu; Xie, Lijun; Zhou, Sufeng; Chen, Juan; Zhao, Yuqing; Deng, Wenjie; Liu, Yun; Zhang, Hongwen; Shao, Feng
• Is Part Of: Clinical pharmacology in drug development. Volume 9:Issue 3(2020)
• Page Start: 346
• Page End: 352
• Publication Date: 2019-10-14
• Subjects: bioequivalence -- narrow‐therapeutic‐index drug -- rivaroxaban -- pharmacokinetic; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.742
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: 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 (AUC0‐t, AUC0‐∞ ), the peak plasma concentration of the drug (Cmax ), time to achieve Cmax, 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 AUC0‐t in fasting conditions and 90.13% to 100.42% in fed conditions. The AUC0‐∞ s were 89.94% to 102.50% and 90.14% to 100.45% under fasting and fed conditions, respectively. The Cmax 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 Cmax 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.