(234) CG100649, a novel dual-acting COX-2 and carbonic anhydrase inhibitor: Multi-dose pharmacokinetics and safety evaluation in healthy male and female subjects

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

“…Repeat dosing schemes of CG100649 in humans produced similarly long plasma t 1/2 of 100 hours (22.5%) and 109 hours (32.7%). 13,14 The long terminal half-live observed for CG100649 in whole blood is in line with the drug-erythrocyte interaction expected from CAinhibitors as a common characteristic. Indeed, methazolamide showed a similarly long t 1/2 .…”

“…The long elimination half‐life found in the present study is consistent with previous studies in humans on file—a mean plasma t 1/2 (%CV) of 111 hours (53.2%) and 133 hours (18.1%) were calculated for single doses of 5 and 12 mg CG100649, respectively. Repeat dosing schemes of CG100649 in humans produced similarly long plasma t 1/2 of 100 hours (22.5%) and 109 hours (32.7%) . The long terminal half‐live observed for CG100649 in whole blood is in line with the drug–erythrocyte interaction expected from CA‐inhibitors as a common characteristic.…”

“…Here, two different loading and maintenance dose regimens were proposed: (i) 2 mg single dose followed by 0.3 mg/day over 30 days; and (ii) 8 mg single dose followed by 1.2 mg/day over 30 days. These dosing schemes were used in prior human studies to attain steady‐state drug concentrations. The purpose of the present study was to test whether the PK model derived for CG100649 from single‐dose exposure would predict steady‐state kinetics in order to inform future patient trials in which chronic dosing is required.…”