Pharmacokinetics and Safety of a Single Dose and Multiple Doses of Allisartan Isoproxil, an Angiotensin II Receptor Blocker, in Healthy Chinese People.

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single- and multiple-dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (Cmax ) of 2242 ± 1037 ng/mL and median time to reach Cmax (Tmax ) of 3.5 hours (2.5-8 hours). The median Tmax, at steady state was 4.0 hours (1.5-8 hours). The mean Cmax at steady state (Cmax, SS ) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the Cmax, SS , area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC0-24 SS ), and AUC0-72 after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days.

Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single-Site, Single-Dose, Randomized, Open, 2-Period, 2-Sequence, Crossover Bioequivalence Study.

Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single-site, single-dose, randomized, open, 2-period, 2-sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography-tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers.

Pharmacokinetics and Safety of Fosaprepitant Dimeglumine in Healthy Chinese Volunteers: Bioequivalence Study.

Fosaprepitant dimeglumine (FD) is a precursor of aprepitant. FD can be metabolized into aprepitant. This randomized, single-center, open, 2-cycle, single-dose, crossover bioequivalence study compared the pharmacokinetics (PK) and safety of intravenously FD of test and reference products in healthy volunteers (HVs). HVs were assigned to the test group or reference group randomly and given FD intravenously. The plasma concentration of FD and aprepitant was measured using liquid chromatography-tandem mass spectrometry. PK parameters were ascertained based on a noncompartmental model. Data for 29 HVs were obtained. The geometric mean and 90% confidence intervals of maximum plasma concentration (Cmax ), area under the concentration-time curve from time 0 to time of last measurable plasma concentration (AUC0-t ), and area from the last datum point to time infinity (AUC0-∞ ) of test and reference groups were 101.69% (95.06%, 108.77%), 103.52% (99.15%, 108.09%), and 105.58% (99.51%, 112.01%), respectively. These 3 parameters were within the acceptance range of 80.0% to 125.00%, and the test product was bioequivalent to the reference product. The coefficient of variation (CV) of Cmax , AUC0-t , and AUC0-∞ was 15.14%, 9.67%, and 11.89%, respectively. Intravenously administered FD provided by 2 sponsors achieved bioequivalence. FD values from test and reference products were bioequivalent. All adverse events were mild and serious adverse events absent in HVs. This study indicated that FD may provide a safer alternative to aprepitant for chemotherapy-induced nausea and vomiting.