Publications
Product
| 지원과제 | cPMTb |
| 저자명 | Cho YS, Bae KS, Choi SC, Cho JM, Lim HS |
| 학회정보 | Clin Ther. 44(1):67-80.e1 / 2022.01 |
| 제 목 | Population Pharmacokinetic and Pharmacodynamic Analysis of Polmacoxib in Healthy Volunteers and Patients With Osteoarthritis |
| LINK | www.ncbi.nlm.nih.gov/pubmed/34974943/ |
| 게시일 | 2025-03-27 14:53:20 |
| 년도 | |
| 내용 | Purpose: Polmacoxib, a new coxib dually inhibiting cyclooxygenase-2 and carbonic anhydrase I/II, was recently approved for osteoarthritis treatment in South Korea. This study explored the population pharmacokinetic and pharmacodynamic characteristics of polmacoxib.
Methods: Nonlinear mixed-effects modeling was performed using pooled pharmacokinetic data from a Phase I study in healthy individuals and pharmacokinetic properties and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) data from a Phase IIb study in patients with osteoarthritis. Pharmacodynamic models for WOMAC were sequentially fit using individual pharmacokinetic parameter estimates. Findings: Polmacoxib concentrations in whole blood were adequately described by the 2-compartment model, with mixed zero- and first-order absorption kinetics. Iron concentration was the significant covariate associated with clearance of polmacoxib. The relationship between the whole blood concentration of polmacoxib and WOMAC was best described by a 2-effect compartment model that consisted of central and peripheral compartments with the rate constant of 0.408 min-1 for distribution to the central effect compartment. A decrease in WOMAC was linked to the central effect site compartment concentration through an ordinary maximum effect model with an effect site concentration needed to achieve 50% of the maximum effect of 508 ng/mL. Implications: The current model accurately characterized the pharmacokinetic and pharmacodynamic properties of polmacoxib and could provide a basis for individualized drug therapy. Keywords: WOMAC; osteoarthritis; pharmacodynamic properties; pharmacokinetic properties; polmacoxib. |
