Population pharmacokinetic and pharmacodynamic modeling of different formulations of ono-5334, cathepsin k inhibitor, in caucasian and japanese postmenopausal females

Chihiro Hasegawa, Tomoya Ohno, Takeo Umemura, Naoki Honda, Michiyo Ohyama, Shinichi Nagase, Maria Small, Steve Deacon, Mikio Ogawa, Ichiro Ieiri

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)23-34
Number of pages12
JournalJournal of Clinical Pharmacology
Volume54
Issue number1
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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