Effect of Food on the Pharmacokinetic Properties of the Oral Sarpogrelate Hydrochloride Controlled-Release Tablet in Healthy Male Korean Subjects

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 C_max and AUC_last 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. T_max 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 C_max and AUC_last, respectively. The drug was well-tolerated by the healthy subjects in this study.