Effect of food on the pharmacokinetic properties of the oral Sarpogrelate Hydrochloride controlled-release tablet in healthy male korean subjects

摘要

Background: A new controlled-release formulation of sarpogrelate, a 5-hydroxytryptamine receptor subtype 2 antagonist that blocks serotonin-induced platelet aggregation, has been developed for once-daily administration. Objective: This study evaluated the effect of food on the pharmacokinetic properties of controlled-release sarpogrelate (sarpogrelate CR) in healthy volunteers. Methods: A randomized, open-label, two-period, two-treatment crossover study was performed in healthy male Korean subjects. Following an overnight fast, a single dose of sarpogrelate CR 300 mg was administered either in the fasted condition or immediately after a high-fat breakfast. Pharmacokinetic parameters were calculated using a noncompartmental analysis. Tolerability was determined using clinical laboratory testing and physical examination, including vital sign measurements, electrocardiography, and interviews with the volunteers regarding adverse events (AEs). Results: A total of 24 healthy subjects were enrolled, 23 of whom completed the study (mean [range] age, 26 years [21-45]; weight, 68.1 kg [56.0-79.9]; body mass index, 22.1 kg/m2 [18.8-25.0]). Sarpogrelate Cmax and AUClast were decreased In the fed condition compared with those in the fasted condition, with geometric mean ratios (90% CI) of 0.4868 (0.4041-0.5864) and 0.7394 (0.6809-0.8028), respectively. Tmax was delayed from 0.75 to 4.0 hours after a high-fat meal, but the fed condition exhibited a similar elimination profile to that of the fasted condition. The most commonly reported AE was headache (n = 2), and other AEs were reported in 1 subject each. All of the AEs were considered mild in intensity, and the participants recovered without treatment. Conclusions: Compared with the administration of sarpogrelate CR 300 mg in the fasted condition, administration with food was associated with a decreased rate and extent of absorption, as assessed by Cmax and AUClast, respectively. The drug was well-tolerated by the healthy subjects in this study.