Clinical Pharmacokinetics of Polmacoxib (CG100649): A Tissue-Selective Dual COX-2 and Carbonic Anhydrase I/II Inhibitor.

Polmacoxib (CG100649; Acelex) is a first-in-class non-steroidal anti-inflammatory drug that combines selective cyclooxygenase-2 (COX-2) inhibition with high-affinity binding to carbonic anhydrase I/II (CA-I/II). Approved for osteoarthritis in South Korea (2015) and India (2023), it exhibits pharmacokinetic (PK) properties distinct from other coxibs. The objective of this review is to review the clinical PK and pharmacokinetic-pharmacodynamic (PK-PD) profile of polmacoxib, compare it with other coxibs, and identify key evidence gaps. PubMed, Embase, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov were searched through June 2026, supplemented by reference lists and regulatory, patent, and Protein Data Bank records. The clinical PK profile of polmacoxib is dominated by erythrocyte sequestration via high-affinity binding to CA-I/II. After oral dosing, whole-blood concentrations exceed plasma concentrations by approximately 50-78 on average, with individual values approaching 120-fold, and terminal half-lives are approximately 121-203 h in blood and 100-167 h in plasma. A 2-compartment whole-blood model with mixed zero- and first-order absorption best describes the data, with serum iron, white-cell count, and age identified as covariates of clearance. The 2-mg once-daily dose substantially inhibits thromboxane B2 and ex vivo PGE2, with only modest, dose-dependent inhibition of urinary prostacyclin metabolite (PGI-M) that is of comparable magnitude, although less sustained, to celecoxib 200 mg after single dosing; the 2-mg dose is noninferior to celecoxib 200 mg on WOMAC pain endpoints in osteoarthritis. Ketoconazole produces only modest changes in plasma exposure, and PK data in hepatic impairment, renal impairment, older people, and non-Korean populations remain limited. Polmacoxib has a unique PK profile among coxibs, driven by erythrocyte carbonic anhydrase binding, which supports its proposed tissue-selective pharmacology. Further studies in special populations, drug-drug interactions, and post-marketing settings are needed to support broader global use.