Population pharmacokinetic and pharmacodynamic modeling of different formulations of ONO-5334, cathepsin K inhibitor, in Caucasian and Japanese postmenopausal females.

摘要: ONO-5334, a selective inhibitor of cathepsin K, is potential new treatment for osteoporosis. The objectives this study were to (1) develop population pharmacokinetic-pharmacodynamic (PK-PD) models ONO-5334 using dose-ascending data from healthy postmenopausal females, (2) examine comparability PK and/or PD profile between Caucasian and Japanese, (3) compare PK-PD immediate release tablet (IRT) sustained (SRT). developed each formulation post-dose levels bone resorption markers (serum CTX NTX). provided 4 phase 1 studies with total 201 94 Japanese subjects. Plasma concentrations thoroughly evaluated in those studies. An indirect response model described relationships plasma ONO-5334. There was no significant difference pharmacodynamic potency (IC50 ) Japanese. Based on the model, serum NTX after administration IRT or SRT simulated, results showed that would provide comparable effect lower dose relative IRT.