Assessment of the Utility of Physiologically-based Pharmacokinetic Model for prediction of Pharmacokinetics in Chinese and Japanese Populations.
Int J Med Sci
; 18(16): 3718-3727, 2021.
Article
em En
| MEDLINE
| ID: mdl-34790045
ABSTRACT
The objective for the present analyses was to evaluate the utility of physiologically-based pharmacokinetic (PBPK) modeling for prediction of the pharmacokinetics (PK) in Chinese and Japanese populations with a panel of Pfizer internal compounds. Twelve compounds from Pfizer internal development pipeline with available Westerner PK data and available PK data in at least one of the subpopulations of Japanese and Chinese populations were identified and included in the current analysis. These selected compounds represent various elimination pathways across different therapeutic areas. The Simcyp® PBPK simulator was used to develop and verify the PBPK models of individual compounds. The developed models for these compounds were verified by using the clinical PK data in Westerners. The verified PBPK models were further used to predict the PK of these compounds in Chinese and Japanese populations and the predicted PK parameters were compared with the observed PK parameters. Ten of the 12 compounds had PK data in Chinese, and all the 12 compounds had PK data in Japanese. In general, the PBPK models performed well in predicting PK in Chinese and Japanese, with 8 of 10 drugs in Chinese and 7 of 12 drugs in Japanese has AAFE values less than 1.25-fold. PBPK-guided predictions of the relative PK difference were successful for 75% and 50%, respectively, between Chinese and Western and between Japanese and Western of the tested drugs using 0.8-1.25 as criteria. In conclusion, well verified PBPK models developed using data from Westerners can be used to predict the PK in Chinese and Japanese populations.
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Texto completo:
1
Temas:
ECOS
/
Aspectos_gerais
Bases de dados:
MEDLINE
Assunto principal:
Farmacocinética
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Taxa de Depuração Metabólica
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Povo Asiático
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Int J Med Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos