ArticleClinical pharmacokinetics2018
Explaining Ethnic Variability of Transporter Substrate Pharmacokinetics in Healthy Asian and Caucasian Subjects with Allele Frequencies of OATP1B1 and BCRP: A Mechanistic Modeling Analysis.
Article in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Inter-ethnic differences in pharmacokinetics-is there more that unites than divides?Pharmacology research & perspectives · 2021Pooled it
- Ethnic Bridging of Sepiapterin in Chinese and Korean Populations Based on Predictions From Genetic Polymorphism of Breast Cancer Resistance Protein.Clinical and translational science · 2026Article
- A Phase 1 Study to Assess the Pharmacokinetics, Food Effect, Safety, and Tolerability of Sepiapterin in Healthy Japanese and Non-Japanese Participants.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Physiologically based pharmacokinetic (PBPK) modeling of pitavastatin in relation to SLCO1B1 genetic polymorphism.Archives of pharmacal research · 2024Article
- Surveys/Research Exploring Japanese Phase I Studies in Global Drug Development: Are They Necessary Prior to Joining Global Clinical Trials?Clinical pharmacology in drug development · 2021Article
- Physiologically Based Pharmacokinetic Modeling of Rosuvastatin to Predict Transporter-Mediated Drug-Drug Interactions.Pharmaceutical research · 2021Article
- Medically Important Alterations in Transport Function and Trafficking of ABCG2.International journal of molecular sciences · 2021Review
- PBPK Model of Coproporphyrin I: Evaluation of the Impact of SLCO1B1 Genotype, Ethnicity, and Sex on its Inter-Individual Variability.CPT: pharmacometrics & systems pharmacology · 2021Article
- Prediction of Drug Clearance from Enzyme and Transporter Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- ABCB1 and ABCG2 Together Limit the Distribution of ABCB1/ABCG2 Substrates to the Human Retina and theFrontiers in pharmacology · 2021Article
- Influence of Drug-Drug Interactions on the Pharmacokinetics of Atorvastatin and Its Major Active Metabolite ortho-OH-Atorvastatin in Aging People Living with HIV.Clinical pharmacokinetics · 2020Article
- Estimating In Vivo Fractional Contribution of OATP1B1 to Human Hepatic Active Uptake by Mechanistically Modeling Pharmacogenetic Data.The AAPS journal · 2019Article
- Organic Ion Transporters and Statin Drug Interactions.Current atherosclerosis reports · 2017Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEthnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, this hypothesis contradicts the data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates.
objectiveThe objective of this study is to evaluate a hypothesis that is physiologically reasonable and more consistent with clinical observations.
methodsWe evaluated if allele frequencies of two transporters (OATP1B1 and BCRP) are key contributors to ethnic variability. In this hypothesis, the same genotype leads to the same activity independent of ethnicity, in contrast to the previous hypothesis of intrinsic ethnic variability in OATP1B1 activity. As a validation, we perform mechanistic pharmacokinetic modeling for SLCO1B1 (encoding OATP1B1) and ABCG2 (encoding BCRP) genotyped pharmacokinetic data from 18 clinical studies with healthy Caucasian and/or Asian subjects.
resultsSimulations based on the current hypothesis reasonably describe SLCO1B1 and ABCG2 genotyped pharmacokinetic time course data for five transporter substrates (atorvastatin, pitavastatin, pravastatin, repaglinide, and rosuvastatin) in Caucasian and Asian populations.
conclusionThis hypothesis covers the observations that can (e.g., ethnic differences in rosuvastatin pharmacokinetics) or cannot (e.g., lack of differences for pitavastatin pharmacokinetics) be explained by the previous hypothesis. It helps to characterize sources of ethnic variability and provides a foundation for predicting ethnic variability in transporter substrate pharmacokinetics.
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Registered trials
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