Comparison of pharmacokinetics between sarpogrelate hydrochloride immediate-release formulation and controlled-release formulation.
OBJECTIVE
Sarpogrelate hydrochloride is a selective 5-hydroxytryptamine receptor subtype 2A (5HT(2A)) antagonist that blocks serotonin-induced platelet aggregation. The aim of this study was to compare the pharmacokinetics of sarpogrelate and its metabolite after dosing with a controlledrelease (CR) formulation or an immediaterelease (IR) formulation.


METHODS
In this open-label, 2-period, 2-treatment crossover study, 36 healthy male subjects were evenly allocated to two groups in a sequence-randomized manner. In the first period, the first group received 100-mg sarpogrelate IR 3 times at a 6-h interval, and the second group received 300-mg sarpogrelate CR once. After a 7-day washout, the two groups switched their dosing schedule. Serial blood sampling was performed up to 24 hours after the first drug administration during each period. Plasma concentrations of sarpogrelate and its metabolite (M-1) were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods.


RESULTS
There were no significant differences between two formulations in the pharmacokinetic properties in the time to reach maximum plasma concentration (C(max)) of sarpogrelate and its metabolite. The CR-to-IR geometric mean ratios, as measured by area under the plasma concentration-time curve (AUC) were 1.31 (90% confidence interval, 1.22 - 1.41) for sarpogrelate and 1.21 (1.14 - 1.29) for M-1. The C(max) was 0.98 (0.85 - 1.12) for sarpogrelate and 1.07 (0.96 - 1.19) for M-1.


CONCLUSIONS
After the administration of sarpogrelate hydrochloride CR and IR formulations using the same daily dose, AUCs were slightly higher for the CR formulation than for the IR formulation for both sarpogrelate and its metabolite M-1, but the C(max) values were similar.
Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
Tae-Eun
TE
Kim
Jung-Ryul
JR
Kim
Jin Ah
JA
Jung
Suk-Ran
SR
Kim
Jae Won
JW
Lee
Hun
H
Jun
Soo-Youn
SY
Lee
Wooseong
W
Huh
Jaewook
J
Ko
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D056910:Republic of Korea; D013386:Succinates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; D013386:Succinates; C064294:sarpogrelate