Pharmacokinetic Modeling Analysis of Cilostazol and its Active Metabolites (OPC-13015 and OPC-13213) after Multiple Oral Doses of Cilostazol in Healthy Korean Volunteers.

Pharmacokinetic Modeling Analysis of Cilostazol and its Active Metabolites (OPC-13015 and OPC-13213) after Multiple Oral Doses of Cilostazol in Healthy Korean Volunteers. Xenobiotica. 2019 Jun 10;:1-26 Authors: Cui A, Kim YH, Ghim JL, Jung JA, Cho SH, Choe S, Choi HY, Bae KS, Lim HS Abstract Cilostazol is a selective inhibitor of PDE III, which is prescribed for patients with peripheral arterial disease, especially intermittent claudication. The purpose of the study was to investigate the PK of cilostazol and its metabolites on the IR formulation of cilostazol in healthy Korean male volunteers by population PK modeling analysis implemented using NONMEM software. A 2 × 2 crossover study comparing multiple oral doses of IR and SR formulations of cilostazol were conducted. Serial plasma concentrations of cilostazol and its active metabolites were used in this analysis and best depicted by one compartment model, with absorption kinetics of cilostazol having mixed first- and zero-order kinetics with a time delay at the beginning of absorption. The introduction of interoccasion variabilities into zero-order (D1), first-order (Ka), and relative bioavailability (F1) significantly improved the model fit, and total body water (TBW) was identified as a significant covariate positively affecting the clearance of cilostazol. The model validation suggested that the model constructed in this study predicted the plasma concentration of cilostaz...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research