ArticleBritish journal of clinical pharmacology2014
Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 4 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons.Frontiers in medicine · 2023Pooled it
- Opioid exposure during pregnancy and the risk of congenital malformation: a meta-analysis of cohort studies.BMC pregnancy and childbirth · 2022Pooled it
- Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.PLoS medicine · 2016Pooled it
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum.Journal of clinical pharmacology · 2019Trial
- Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.Clinical pharmacology and therapeutics · 2026Review
- Physiologically-based pharmacokinetic modelling of uridine 5'-diphosphoglucorosultransferase (UGT) substrate drugs in pregnant women.British journal of clinical pharmacology · 2026Article
- Pharmacometric modeling of opioid disposition in pregnancy: a systematic review of PopPK and PBPK approaches, model limitations, and future directions.Frontiers in pharmacology · 2026Review
- Rosuvastatin PBPK Modeling: Incorporating Liver Concentrations and Effects of Ethnicity, Genetic Polymorphisms, Lactone Formation, DDI and Pregnancy.CPT: pharmacometrics & systems pharmacology · 2025Article
- Physiologically Based Pharmacokinetic Model for Prediction of Immunoglobulins Exposure in Pregnant Women.Antibodies (Basel, Switzerland) · 2025Article
- Determining the Optimal Dosing of Methyldopa in Pregnancy-Induced Hypertension Using PBPK-PD Modeling.Clinical pharmacokinetics · 2025Article
- Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy.British journal of clinical pharmacology · 2025Article
- Labetalol Dosing in Pregnancy: PBPK/PD and CYP2C19 Polymorphisms.Journal of clinical pharmacology · 2024Article
- PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.Pharmaceutics · 2024Article
- The effect of pregnancy-related hormones on hepatic transporters: studies with premenopausal human hepatocytes.Frontiers in pharmacology · 2024Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Review
- P-glycoprotein efflux transporter: a key to pharmacokinetic modeling for methadone clearance in fetuses.Frontiers in pharmacology · 2023Article
- Predicting Human Fetal Drug Exposure Through Maternal-Fetal PBPK Modeling and In Vitro or Ex Vivo Studies.Journal of clinical pharmacology · 2022Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimConducting PK studies in pregnant women is challenging. Therefore, we asked if a physiologically-based pharmacokinetic (PBPK) model could be used to predict the disposition in pregnant women of drugs cleared by multiple CYP enzymes.
methodsWe expanded and verified our previously published pregnancy PBPK model by incorporating hepatic CYP2B6 induction (based on in vitro data), CYP2C9 induction (based on phenytoin PK) and CYP2C19 suppression (based on proguanil PK), into the model. This model accounted for gestational age-dependent changes in maternal physiology and hepatic CYP3A, CYP1A2 and CYP2D6 activity. For verification, the pregnancy-related changes in the disposition of methadone (cleared by CYP2B6, 3A and 2C19) and glyburide (cleared by CYP3A, 2C9 and 2C19) were predicted.
resultsPredicted mean post-partum to second trimester (PP : T2 ) ratios of methadone AUC, Cmax and Cmin were 1.9, 1.7 and 2.0, vs. observed values 2.0, 2.0 and 2.6, respectively. Predicted mean post-partum to third trimester (PP : T3 ) ratios of methadone AUC, Cmax and Cmin were 2.1, 2.0 and 2.4, vs. observed values 1.7, 1.7 and 1.8, respectively. Predicted PP : T3 ratios of glyburide AUC, Cmax and Cmin were 2.6, 2.2 and 7.0 vs. observed values 2.1, 2.2 and 3.2, respectively.
conclusionsOur PBPK model integrating prior physiological knowledge, in vitro and in vivo data, allowed successful prediction of methadone and glyburide disposition during pregnancy. We propose this expanded PBPK model can be used to evaluate different dosing scenarios, during pregnancy, of drugs cleared by single or multiple CYP enzymes.
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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.