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Background and Objectives Ezetimibe/simvastatin combination tablet has been approved for the treatment of high low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia or mixed hypercholesterolaemia as adjunctive therapy to diet, when diet alone is insufficient in lowering cholesterol. The aims of this study were to assess the pharmacokinetics and safety of an ezetimibe/simvastatin combination tablet after oral single-dose administration in healthy Chinese subjects including sex-related differences in pharmacokinetics. Methods This was an open-label, single-dose study. Twelve healthy subjects (six males and six females) received a single dose of an ezetimibe/simvastatin combination tablet (ezetimibe 10 mg and simvastatin 40 mg). The pharmacokinetic parameters for ezetimibe and simvastatin were assessed by determining total ezetimibe, free ezetimibe, simvastatin and simvastatin acid concentrations using a validated liquid chromatography-tandem mass spectrometry method. Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations and 12-lead electrocardiograms. Results The pharmacokinetic parameters (mean ± SD) for total ezetimibe and free ezetimibe following a single dose were: maximum plasma drug concentration (Cmax) 81.56 ± 26.62 and 9.40 ± 6.17 ng/mL; time to reach Cmax (tmax) 0.93 ± 0.30 and 1.25 ± 1.27 h; elimination half-life (t1/2) 24.32 ± 13.27 and 18.90 ± 9.66 h, and mean area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast) 579.06 ± 241.45 and 126.01 ± 69.01 ng⋅h/mL, respectively. The pharmacokinetic parameters (mean ± SD) for simvastatin and simvastatin acid following a single dose were: Cmax 11.92 ± 5.50 and 3.37 ± 1.78 ng/mL, tmax 0.98 ± 0.28 and 3.73 ± 1.68 h, t1/2 4.19 ± 1.81 and 7.65 ± 7.96 h, and mean AUClast 33.63 ± 20.41 and 32.50 ± 18.79 ng⋅h/mL. Higher AUClast and AUC from time zero to infinity (AUC∞), and lower apparent total body clearance of drug from plasma after oral administration (CL/F) for total ezetimibe and free ezetimibe were observed in female subjects compared with those in male subjects. There were no differences between the pharmacokinetic parameters of simvastatin and simvastatin acid for female and male subjects in the study. Conclusion Ezetimibe/simvastatin combination tablet has a generally favourable safety and tolerability profile in healthy Chinese subjects. A statistically significant difference with regard to sex in the pharmacokinetics of ezetimibe was observed. Sex had no effect on the pharmacokinetics of simvastatin and simvastatin acid. [ABSTRACT FROM AUTHOR]

Background and objective: Olopatadine is a new selective histamine H1 receptor antagonist with anti-inflammatory and anti-allergic effects. Its pharmacokinetics and safety have not previously been evaluated in Chinese subjects. The aims of this study were to assess the pharmacokinetics and safety of olopatadine after single- and multiple-dose oral administration in healthy Chinese subjects and to identify any differences in pharmacokinetics between males and females. Methods: The pharmacokinetic parameters for olopatadine in 12 healthy Chinese subjects (six males and six females) were assessed by determining olopatadine concentrations with a validated liquid chromatography-tandem mass spectrometry method. Safety and tolerability were evaluated by monitoring adverse events, laboratory assay results, vital signs, physical examination findings and 12-lead ECG results. Results: The pharmacokinetic parameters (mean± SD) for olopatadine following a single dose were: maximum plasma concentration (Cmax) 69.98± 20.87ng/mL, time to reach Cmax (tmax) 1.02±0.34h, elimination half-life (t%) 5.87±4.24h, area under the plasma-concentration curve (AUC) from time zero to the time of last quantifiable concentration (AUClast) 266.00±143.95ng•h/mL, AUC from time zero extrapolated to infinity (AUCo,) 283.46 ± 152.96 ng• h/mL, apparent oral clearance (CL/F) 23.45 ± 12.59 L/h and apparent volume ofdistribution after oral administration (Vd/F) 133.83 + 43.07 L. The pharmacokinetic parameters of olopatadine after multiple doses were similar to those after a single dose. In both studies, significantly higher AUClast, AUC∞ and Cmax, longer t½ (single-dose only) and lower CL/F were observed in female subjects compared with male subjects after both single and multiple dosing. No serious adverse events occurred. Conclusion: Olopatadine was shown to be safe and well tolerated in healthy Chinese subjects. There were no changes in absorption and elimination of olopatadine following multiple doses and no accumulation was found. Possible sex-related differences in absorption and elimination of olopatadine were observed. [ABSTRACT FROM AUTHOR]