PIII‐42

PURPOSE To evaluate single and multiple dose pharmacokinetics of PRX‐00023, a novel non‐azapirone 5HT1A agonist in healthy subjects. METHODS In the first in human single ascending dose study, 36 healthy subjects received oral doses (10 mg to 60 mg) of PRX‐00023. In two multiple dose studies healthy subjects received oral doses of 10 to150 mg QD for up to 28 days. The effect of a high fat meal on PRX‐00023 pharmacokinetics was explored at the 150 mg dose in a fixed sequential cross‐over manner. Serum concentrations were determined for pharmacokinetics using a validated LC/MS/MS method. RESULTS Serum exposures (AUC 0‐∞ , AUC 0–24 and C max ) increased in a dose proportional manner following single and multiple oral PRX‐00023 administration. The terminal half‐life ranged from 10 to 14 hours suggesting the feasibility of a once daily dosing regimen. Administration of PRX‐00023 with a high fat meal decreased the C max by ∼26% and had a negligible effect on AUC 0–24 (increased < 5%), relative to administration in the fasted state. CONCLUSIONS The pharmacokinetic profile of PRX‐00023 from this study is consistent with once daily dosing, as compared with azapirone drugs which typically have short half lives. In addition, the preliminary food‐effect data indicate that PRX‐00023 may be administered with or without food. Clinical Pharmacology & Therapeutics (2005) 79 , P69–P69; doi: 10.1016/j.clpt.2005.12.250