논문/저서
| Population Pharmacokinetic and Pharmacodynamic Analysis of Polmacoxib in Healthy Volunteers and Patients With Osteoarthritis | ||
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Clin Ther. 2022 Jan;44(1):67-80.e1. doi: 10.1016/j.clinthera.2021.11.008. Epub 2021 Dec 31.
Yong-Soon Cho, Kyun-Seop Bae, Seung Chan Choi, Joong Myung Cho, Hyeong-Seok Lim
Abstract
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.
PMID: 34974943 DOI: 10.1016/j.clinthera.2021.11.008 |
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