Abstract
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.
Key words
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Article info
Publication history
Published online: December 31, 2021
Accepted:
November 15,
2021
Identification
Copyright
© 2021 Elsevier Inc.
