ArticleCPT: pharmacometrics & systems pharmacology2016
Towards a Best Practice Approach in PBPK Modeling: Case Example of Developing a Unified Efavirenz Model Accounting for Induction of CYPs 3A4 and 2B6.
Article in CPT: pharmacometrics & systems pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Predicting Efavirenz Concentrations in the Brain Tissue of HIV-Infected Individuals and Exploring their Relationship to Neurocognitive Impairment.Clinical and translational science · 2019Trial
- Physiologically Based Pharmacokinetic Modeling to Assess Antiretroviral-BTK Inhibitor Interactions and Provide Recommendations for Co-Administration Regimens.Pharmaceutics · 2026Article
- Quantitative systems toxicology approach that integrates PBPK and core hepatic metabolism: a case study with valproic acid.Frontiers in pharmacology · 2026Article
- PBPK Modeling to Recommend Nevirapine Dosing in HIV and HIV-TB Co-infected Patients: Leveraging Enzyme Auto-Induction, Drug Interactions, and Ethnic Variability.The AAPS journal · 2025Article
- A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant.Pharmaceutics · 2024Article
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- PBPK perspective on alternative CYP3A4 inducers for rifampin.CPT: pharmacometrics & systems pharmacology · 2022Article
- Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations.Pharmaceutics · 2022Article
- Prediction of CYP-mediated DDIs involving inhibition: Approaches to address the requirements for system qualification of the Simcyp Simulator.CPT: pharmacometrics & systems pharmacology · 2022Article
- Addressing drug safety of maternal therapy during breastfeeding using physiologically-based pharmacokinetic modeling.CPT: pharmacometrics & systems pharmacology · 2022Article
- Potential drug-drug interaction of olverembatinib (HQP1351) using physiologically based pharmacokinetic models.Frontiers in pharmacology · 2022Article
- Physiologically-Based Pharmacokinetic Modeling to Support the Clinical Management of Drug-Drug Interactions With Bictegravir.Clinical pharmacology and therapeutics · 2021Article
- Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development.AAPS PharmSciTech · 2021Review
- Comprehensive PBPK model to predict drug interaction potential of Zanubrutinib as a victim or perpetrator.CPT: pharmacometrics & systems pharmacology · 2021Article
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- Prediction of the exposure to a 400-mg daily dose of efavirenz in pregnancy: is this dose adequate in extensive metabolisers of CYP2B6?European journal of clinical pharmacology · 2020Article
- Predicting Clinical Effects of CYP3A4 Modulators on Abemaciclib and Active Metabolites Exposure Using Physiologically Based Pharmacokinetic Modeling.Journal of clinical pharmacology · 2020Article
- Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly.Clinical pharmacokinetics · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we present efavirenz physiologically based pharmacokinetic (PBPK) model development as an example of our best practice approach that uses a stepwise approach to verify the different components of the model. First, a PBPK model for efavirenz incorporating in vitro and clinical pharmacokinetic (PK) data was developed to predict exposure following multiple dosing (600 mg q.d.). Alfentanil i.v. and p.o. drug-drug interaction (DDI) studies were utilized to evaluate and refine the CYP3A4 induction component in the liver and gut. Next, independent DDI studies with substrates of CYP3A4 (maraviroc, atazanavir, and clarithromycin) and CYP2B6 (bupropion) verified the induction components of the model (area under the curve [AUC] ratios within 1.0-1.7-fold of observed). Finally, the model was refined to incorporate the fractional contribution of enzymes, including CYP2B6, propagating autoinduction into the model (Racc 1.7 vs. 1.7 observed). This validated mechanistic model can now be applied in clinical pharmacology studies to prospectively assess both the victim and perpetrator DDI potential of efavirenz.
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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.