GCG100649, A Novel Cyclooxygenase‐2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase‐I/II: Preliminary Dose–Exposure Relationships to Define Clinical Development Strategies. Issue 4 (25th July 2013)

• Record Type: Journal Article
• Authors: Hirankarn, Sarapee; Barrett, Jeffrey S.; Alamuddin, Naji; FitzGerald, Garret A.; Skarke, Carsten
• Is Part Of: Clinical pharmacology in drug development. Volume 2:Issue 4(2013:Oct.)
• Page Start: 379
• Page End: 386
• Publication Date: 2013-07-25
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.47
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd47-sec-0001" sec-type="section"> <p>CG100649, proposed as a dual inhibitor of cyclooxygenase (COX)‐2 and carbonic anhydrase (CA)‐I/‐II, is long‐lived in plasma and whole blood. The mean ± SD half‐lives were 131 ± 19 and 127 ± 33 hours, respectively, after administration of oral single doses of 2 or 8 mg CG100649 to healthy volunteers. The whole blood to plasma concentration ratio (78 ± 23) for CG100649 is linear over the dosing interval reflecting a biodistribution pattern consistent with other strong CA‐inhibitors (e.g., acetazolamide, methazolamide). A one compartment model with first order absorption and elimination described CG100649 concentration‐time profiles well. Estimates (%relative SD) between plasma and whole blood were in agreement for the absorption rate constant, 1.54 (58.6) and 1.43 (28.0) hour⁻¹, respectively, but considerably different for clearance, 3.29 (10.4) and 0.04 (7.7) L/h/70 kg, and for volume of distribution, 559 (6.7) and 7.6 (2.4) L/70 kg, respectively. The extent to which these unique PK characteristics of CG100649 discriminate it from other COX‐2 inhibitors will be the subject of future investigation.</p> </sec> </abstract>