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Clinical Drug Investigation

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01-03-2017 | Original Research Article

Quantifying the Exposure of Tapentadol Extended Release in Japanese Patients with Cancer Pain and Bridging Tapentadol Pharmacokinetics Across Populations Using a Modeling Approach

Authors: Liping Zhang, Xiaoyu Yan, Sayori Nobe, Peter Zannikos, Mila Etropolski, Partha Nandy

Published in: Clinical Drug Investigation | Issue 3/2017

Abstract

Background and Objectives

Tapentadol extended release (ER) is approved for the management of chronic and acute pain in adults. There has been no report of tapentadol ER pharmacokinetics in subjects with cancer pain. This analysis investigated tapentadol ER pharmacokinetics in Japanese patients with cancer pain and bridged it with the pharmacokinetics in Japanese healthy subjects and Caucasian patients with cancer pain.

Methods

Nonlinear mixed-effect pharmacokinetic modeling was conducted based on pooled tapentadol ER concentration data collected in five Phase 1 studies from 138 Japanese and Korean healthy subjects and in two Phase 3 studies from 215 Japanese and Korean subjects with cancer pain. Expected tapentadol exposure in subjects with different characteristics was assessed via simulation. Tapentadol ER exposures in Caucasian populations were compared with those in corresponding Japanese populations.

Results

Tapentadol ER pharmacokinetics in Japanese cancer-pain patients were adequately described by a time-invariant, one-compartment disposition model with two input functions and first-order elimination. Weight, age, and albumin were identified as statistically significant covariates, but do not warrant dose adjustment. Comparable pharmacokinetics were shown between Japanese healthy and Caucasian healthy subjects, and between Japanese cancer-pain patients and Caucasian cancer-pain patients.

Conclusion

The apparent differences in the estimated individual pharmacokinetic parameters in Japanese healthy subjects and Japanese cancer-pain patients taking tapentadol ER were explained by covariates incorporated in a unified pharmacokinetic model. Population modeling was essential in this cross-population bridging analysis.

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Title: Quantifying the Exposure of Tapentadol Extended Release in Japanese Patients with Cancer Pain and Bridging Tapentadol Pharmacokinetics Across Populations Using a Modeling Approach
Authors: Liping Zhang
Xiaoyu Yan
Sayori Nobe
Peter Zannikos
Mila Etropolski
Partha Nandy
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 3/2017
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.1007/s40261-016-0482-z

Keynote webinar | Spotlight on medication adherence

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Quantifying the Exposure of Tapentadol Extended Release in Japanese Patients with Cancer Pain and Bridging Tapentadol Pharmacokinetics Across Populations Using a Modeling Approach

Abstract

Background and Objectives

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusion

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