ArticleJournal of pharmaceutical analysis2023
Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics.
Article in Journal of pharmaceutical analysis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 6 citations in OpenAlex.
- Characterization of preclinical radio ADME properties of ARV-471 for predicting human PK using PBPK modeling.Journal of pharmaceutical analysis · 2025Article
- Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
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3 authors at 2 institutions in 1 country.
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Abstract
Fexofenadine is useful in various allergic disease treatment. However, the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking. This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability. Polymorphisms of the organic-anion-transporting-polypeptide (OATP) 1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity. Therefore, modeling was performed using fexofenadine oral exposure data according to the OATP1B1- and 2B1-polymorphisms. OATP1B1 and 2B1 were identified as effective covariates of clearance (CL/F) and distribution volume (V/F)-CL/F, respectively, in fexofenadine pharmacokinetic variability. CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17- and 2.20-folds, respectively, depending on the OATP1B1 polymorphism. Among the individuals with different OATP2B1 polymorphisms, the CL/F and V/F differed by up to 1.73- and 2.00-folds, respectively. Ratio of the areas under the curves following single- and multiple-administrations, and the cumulative ratio were significantly different between OATP1B1- and 2B1-polymorphism groups. Based on quantitative prediction comparison through a model-based approach, OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability. Based on the established pharmacokinetic-pharmacodynamic relationship, the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25- and 0.87-times, respectively, and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well. This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.
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