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The effects of food on the pharmacokinetics (PKs) and safety of 10‐mg rivaroxaban tablets in healthy Chinese subjects were investigated from 1 bioequivalence trial. The bioequivalence trial was designed as randomized, open‐label, 2‐sequence, 4‐period crossover under both fasted and fed conditions. A total of 56 healthy subjects were enrolled, 62.5% were male. These subjects received a single oral 10‐mg dose of rivaroxaban with a 7‐day washout between 4 periods. Serial PK samples were collected and plasma concentrations were analyzed using validated high‐performance liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods. The BE module of WinNonLin was used for statistical analysis of the maximum concentration (Cmax), the area under the concentration–time curve from zero to the final measurable concentration (AUC0‐t), and the area under the concentration–time curve from time zero to infinity (AUC0‐∞) of rivaroxaban in plasma. Compared with the fasted state, the Cmax, AUC0‐t, and AUC0‐∞ of rivaroxaban significantly increased by 47%, 28%, and 26%, respectively, with oral administration of rivaroxaban 10 mg in the fed state. The incidence of adverse events (AEs) was similar between the fasted and fed states, and no serious AEs were observed. Food significantly increased the exposure to rivaroxaban 10 mg in Chinese subjects. [ABSTRACT FROM AUTHOR]

Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under fasting and postprandial conditions. Participants were randomly divided into three sequences at a ratio of 1:1:1 for three-cycle, reference formulation replicated, crossover administration. The average bioequivalence (ABE) and reference-scaled average bioequivalence (RSABE) methods were used to evaluate BE using the main pharmacokinetic (PK) parameters. Overall, 45 eligible participants were enrolled in the postprandial trial, which was consistent with the fasting trial. For valsartan, the RSABE method was used to evaluate the BE of C max , while the ABE method was applied to evaluate the BE of AUC 0-t and AUC 0-∞ . Both point estimates and 95% upper confidence bound met the BE criteria. For amlodipine, the ABE method was performed, and the 90% confidence intervals of the geometric mean ratios (GMR) for C max and AUC 0-72 h were all within 80%-125%, with the BE criteria being met. Therefore, the two formulations are bioequivalent and have similar safety profiles in healthy Chinese subjects. Clinical trial registration: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20210214]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qiu, Song, Ding, Sun, Du, Yang, Bai and Dong.)

Context: Atorvastatin (ATV) and QiShenYiQi pills (QSYQ), a Chinese patent medicine, are often co-prescribed to Chinese cardiovascular patients. The effects of QSYQ on the pharmacokinetics of ATV have not been studied., Objective: We investigated the influence of QSYQ on the pharmacokinetics of ATV and its metabolites upon oral or intravenous administration of ATV to rats., Materials and Methods: Sprague-Dawley rats ( n  = 5/group) were pre-treated with oral QSYQ (675 mg/kg) or vehicle control for 7 days and then orally administrated ATV (10 mg/kg) or intravenously administrated ATV (2 mg/kg). Serum concentrations of ATV and metabolites were determined by ultra-high performance liquid chromatography tandem mass spectrometry. Expression of metabolic enzymes and transporters in jejunum and ileum were measured by quantitative real-time PCR and Western blot., Results: QSYQ resulted in an increase of AUC 0-12 h of ATV from 226.67 ± 42.11 to 408.70 ± 161.75 ng/mL/h and of C max of ATV from 101.46 ± 26.18 to 198.00 ± 51.69 ng/mL and in an increased of para- hydroxy atorvastatin from 9.07 ± 6.20 to 23.10 ± 8.70 ng/mL in rats administered ATV orally. No change was observed in rats treated intravenously. The expression of multidrug resistance-associated protein 2 mRNA and protein decreased in ileum, and the mRNA of P-glycoprotein decreased in jejunum, though no change in protein expression was found., Discussion and Conclusions: QSYQ increased bioavailability of ATV administered orally through inhibiting the expression of Mrp2 in ileum. Clinicians should pay close attention to potential drug-drug interactions between ATV and QSYQ.