Effect of food intake on the pharmacokinetics of sarpogrelate and its active metabolite following oral administration to beagle dogs

Abstract

1. The objectives of this study were to develop a pharmacokinetic model for sarpogrelate and its metabolite M-1 and to identify the effect of food on sarpogrelate and M-1 pharmacokinetics in beagle dogs.

2. A single 100 mg oral dose of sarpogrelate was administered to fasted and fed beagle dogs and the plasma concentrations of sarpogrelate and M-1 were measured simultaneously by liquid chromatography tandem mass spectrometry. The resultant data were analyzed by modeling approaches using ADAPT5.

3. The plasma concentration time course of sarpogrelate and M-1 were described using a parent-metabolite compartment model with first-order absorption and elimination. The systemic exposure of sarpogrelate and its metabolite after the administration of a single 100 mg oral dose was significantly decreased under the fed condition compared to that under the fasting condition. Modeling approaches have sufficiently explained the food effect of sarpogrelate, i.e. an increased V_c and decreased K_a, in fed dogs. The food effect of sarpogrelate was due to its pH-dependent dissolution.

4. These findings suggest that food intake affects both the rate and extent of absorption of sarpogrelate, and that the pharmacological effect of sarpogrelate can differ significantly according to food intake.

• Compartmental
• food effect
• metabolite
• pharmacokinetics
• sarpogrelate

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Erratum