ReviewPharmaceutics2021
PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.
Review in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Disposition and Absolute Bioavailability of Oral Imlunestrant in Healthy Women: A Phase 1, Open-Label Study.Clinical pharmacology in drug development · 2025Article
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- The Absorption, Distribution, Metabolism, and Excretion of Binimetinib Following a Single Oral Dose of [Pharmacology research & perspectives · 2025Article
- Physiologically-Based Pharmacokinetics and Empirical Pharmacodynamic Modeling for Pediatric Henagliflozin Dosing: Clinical Insights for Chinese Patients.Pediatric diabetes · 2025Article
- Article
- HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus‑Based In Vivo Prediction in Humans: Part II.AAPS PharmSciTech · 2024Article
- HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus-Based In Vivo Prediction in Humans: Part I.AAPS PharmSciTech · 2024Article
- Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Avapritinib Carries the Risk of Drug InteractionCurrent drug metabolism · 2024Article
- The Role of "Physiologically Based Pharmacokinetic Model (PBPK)" New Approach Methodology (NAM) in Pharmaceuticals and Environmental Chemical Risk Assessment.International journal of environmental research and public health · 2023Review
- Prediction of trough concentration and ALK occupancy in plasma and cerebrospinal fluid using physiologically based pharmacokinetic modeling of crizotinib, alectinib, and lorlatinib.Frontiers in pharmacology · 2023Article
- Prediction for optimal dosage of pazopanib under various clinical situations using physiologically based pharmacokinetic modeling.Frontiers in pharmacology · 2022Article
- Editorial: Pharmacokinetic evaluation and modeling of clinically significant drug metabolites, Volume II.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well studied. This work assesses physiologically based pharmacokinetic (PBPK) modeling as a tool for predicting intestinal metabolism due to UGTs in the human gastrointestinal tract. Available data for intestinal UGT expression levels and in vitro approaches that can be used to predict intestinal metabolism of UGT substrates are reviewed. Human PBPK models for UGT substrates with varying extents of UGT-mediated intestinal metabolism (lorazepam, oxazepam, naloxone, zidovudine, cabotegravir, raltegravir, and dolutegravir) have demonstrated utility for predicting the extent of intestinal metabolism. Drug-drug interactions (DDIs) of UGT1A1 substrates dolutegravir and raltegravir with UGT1A1 inhibitor atazanavir have been simulated, and the role of intestinal metabolism in these clinical DDIs examined. Utility of an in silico tool for predicting substrate specificity for UGTs is discussed. Improved in vitro tools to study metabolism for UGT compounds, such as coculture models for low clearance compounds and better understanding of optimal conditions for in vitro studies, may provide an opportunity for improved in vitro-in vivo extrapolation (IVIVE) and prospective predictions. PBPK modeling shows promise as a useful tool for predicting intestinal metabolism for UGT substrates.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.