ArticleEuropean journal of drug metabolism and pharmacokinetics2018
Physiologically Based Pharmacokinetic Modelling of Cytochrome P450 2C9-Related Tolbutamide Drug Interactions with Sulfaphenazole and Tasisulam.
Article in European journal of drug metabolism and pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 11 citations in OpenAlex.
- Development of physiologically based liver distribution model that incorporates intracellular lipid partitioning and binding to fatty acid binding protein 1.The Journal of pharmacology and experimental therapeutics · 2026Article
- Efavirenz and CYP2C9 Genetic Polymorphisms Reduce CYP2C9 Activity in Healthy Participants.Clinical and translational science · 2026Article
- Development of Physiologically Based Liver Distribution Model that Incorporates Intracellular Lipid Partitioning and Binding to Fatty Acid Binding Protein 1 (FABP1).bioRxiv : the preprint server for biology · 2026Article
- Physiologically Based Pharmacokinetic Modeling to Assess Perpetrator and Victim Cytochrome P450 2C Induction Risk.Pharmaceutics · 2025Article
- An Extensively Humanized Mouse Model to Predict Pathways of Drug Disposition and Drug/Drug Interactions, and to Facilitate Design of Clinical Trials.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Modeling Drug Disposition and Drug-Drug Interactions Through Hypothesis-Driven Physiologically Based Pharmacokinetics: a Reversal Translation Perspective.European journal of drug metabolism and pharmacokinetics · 2018Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCytochrome P450 2C9 (CYP2C9) is involved in the biotransformation of many commonly used drugs, and significant drug interactions have been reported for CYP2C9 substrates. Previously published physiologically based pharmacokinetic (PBPK) models of tolbutamide are based on an assumption that its metabolic clearance is exclusively through CYP2C9; however, many studies indicate that CYP2C9 metabolism is only responsible for 80-90% of the total clearance. Therefore, these models are not useful for predicting the magnitude of CYP2C9 drug-drug interactions (DDIs). This paper describes the development and verification of SimCYP
methodsA PBPK model was optimized in SimCYP
resultsThe optimized tolbutamide model accurately predicted the magnitude of tolbutamide AUC increase (5.3-6.2-fold) reported for sulfaphenazole. Furthermore, the PBPK simulations in a healthy volunteer population adequately predicted the increase in plasma exposure of tolbutamide in patients with cancer (predicted AUC ratio = 4.7-5.4; measured mean AUC ratio = 5.7).
conclusionsThis optimized tolbutamide PBPK model was verified with two strong CYP2C9 inhibitors and can be applied to the prediction of CYP2C9 interactions for novel inhibitors. Furthermore, this work highlights the utility of mechanistic models in navigating the challenges in conducting clinical pharmacology studies in cancer patients.
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