Pharmacokinetics of Orally Administered Single- and Multiple-Dose Olopatadine in Healthy Chinese Subjects

Abstract

Olopatadine is a new selective histamine H(1) 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. 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. The pharmacokinetic parameters (mean +/- SD) for olopatadine following a single dose were: maximum plasma concentration (C(max)) 69.98 +/-20.87 ng/mL, time to reach C(max) (t(max)) 1.02 +/- 0.34 h, elimination half-life (t1/2) 5.87 +/- 4.24 h, area under the plasma-concentration curve (AUC) from time zero to the time of last quantifiable concentration (AUC(last)) 266.00 +/- 143.95 ng.h/mL, AUC from time zero extrapolated to infinity (AUC(infinity)) 283.46 +/- 152.96 ng.h/mL, apparent oral clearance (CL/F) 23.45 +/- 12.59 L/h and apparent volume of distribution after oral administration (V(d)/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 AUC(last), AUC(infinity) and C(max), longer t1/2 (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. 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.