Physiologically based pharmacokinetic modeling to predict exposures in healthy Japanese subjects with different CYP2C19 phenotypes: Esomeprazole case study
| Autor: | Katsuomi Ichikawa, Hitoshi Shimada, Diansong Zhou, Mitsuo Higashimori |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
050101 languages & linguistics
medicine.medical_specialty Physiologically based pharmacokinetic modelling Genotype Population Pharmacokinetic modeling 02 engineering and technology CYP2C19 Gastroenterology Esomeprazole Asian People Japan Pharmacokinetics Internal medicine 0202 electrical engineering electronic engineering information engineering medicine Humans 0501 psychology and cognitive sciences Pharmacology (medical) education Pharmacology education.field_of_study business.industry 05 social sciences Japanese population Cytochrome P-450 CYP2C19 Phenotype 020201 artificial intelligence & image processing business medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 58:29-36 |
| ISSN: | 0946-1965 |
| DOI: | 10.5414/cp203488 |
| Popis: | Purpose The objective of this study was to improve the predictive performance of cytochrome P450 (CYP) 2C19 substrates in Japanese subjects using physiologically based pharmacokinetic (PBPK) modeling. Materials and methods Esomeprazole, a CYP2C19 substrate, was selected as a test compound, and the Simcyp simulator was used for pharmacokinetic prediction. The compound file of esomeprazole model developed in healthy Caucasian subjects was applied directly. The population file "Sim-Japanese" in Simcyp was adopted to predict esomeprazole pharmacokinetics in Japanese, while CYP2C19 enzyme abundances in the liver and the gastrointestinal tract for homozygous extensive metabolizers (homo EMs), heterozygous extensive metabolizers (hetero EMs), and poor metabolizers (PMs) were adjusted to be the same as in Caucasians. Results The PBPK model predicted esomeprazole exposure after 10-, 20-, and 40-mg doses in Japanese subjects within 1.5-fold of observed values in all three -CYP2C19 phenotypes. The reported concentration-time profiles were mostly well-captured within the 95% prediction intervals. Conclusion By adjusting CYP2C19 enzyme abundances levels in the Japanese population, the systemic exposure of esomeprazole in Japanese subjects can be reasonably extrapolated using a PBPK model developed in Caucasian subjects. This analysis serves as a case application for assessing the predictive performance of CYP2C19 substrate in Japanese subjects by using PBPK modeling approach. |
| Databáze: | OpenAIRE |
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