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

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)23-34
ページ数12
ジャーナルJournal of Clinical Pharmacology
54
発行部数1
DOI
出版物ステータス出版済み - 1 1 2014
外部発表Yes

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Cathepsins
Tablets
Pharmacokinetics
Bone Resorption
Population
Cathepsin K
Inhibitory Concentration 50
Osteoporosis
ONO-5334
Biomarkers
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

これを引用

Population pharmacokinetic and pharmacodynamic modeling of different formulations of ono-5334, cathepsin k inhibitor, in caucasian and japanese postmenopausal females. / Hasegawa, Chihiro; Ohno, Tomoya; Umemura, Takeo; Honda, Naoki; Ohyama, Michiyo; Nagase, Shinichi; Small, Maria; Deacon, Steve; Ogawa, Mikio; Ieiri, Ichiro.

:: Journal of Clinical Pharmacology, 巻 54, 番号 1, 01.01.2014, p. 23-34.

研究成果: ジャーナルへの寄稿記事

Hasegawa, Chihiro ; Ohno, Tomoya ; Umemura, Takeo ; Honda, Naoki ; Ohyama, Michiyo ; Nagase, Shinichi ; Small, Maria ; Deacon, Steve ; Ogawa, Mikio ; Ieiri, Ichiro. / Population pharmacokinetic and pharmacodynamic modeling of different formulations of ono-5334, cathepsin k inhibitor, in caucasian and japanese postmenopausal females. :: Journal of Clinical Pharmacology. 2014 ; 巻 54, 番号 1. pp. 23-34.
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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.",
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AU - Nagase, Shinichi

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