ArticleJournal of pharmacokinetics and pharmacodynamics2010
Lumping of physiologically-based pharmacokinetic models and a mechanistic derivation of classical compartmental models.
Article in Journal of pharmacokinetics and pharmacodynamics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled 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
- Best Practices in Physiologically Based Pharmacokinetic (PBPK) Modeling.CPT: pharmacometrics & systems pharmacology · 2026Review
- Tackling High Dimensionality in QSP: Guiding Model Order Reduction With Index Analysis.CPT: pharmacometrics & systems pharmacology · 2026Article
- A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.Molecular pharmaceutics · 2024Article
- Parameter grouping and co-estimation in physiologically based kinetic models using genetic algorithms.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat.Archives of toxicology · 2023Article
- Process and System Clearances in Pharmacokinetic Models: Our Basic Clearance Concepts Are Correct.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Investigation of simplified physiologically-based pharmacokinetic models in rat and human.CPT: pharmacometrics & systems pharmacology · 2023Article
- A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.Frontiers in pharmacology · 2023Article
- High-Dosage Fosfomycin Results in Adequate Plasma and Target-Site Exposure in Morbidly Obese and Nonobese Nonhyperfiltration Patients.Antimicrobial agents and chemotherapy · 2022Article
- A compatibility evaluation between the physiologically based pharmacokinetic (PBPK) model and the compartmental PK model using the lumping method with real cases.Frontiers in pharmacology · 2022Article
- Similar Piperacillin/Tazobactam Target Attainment in Obese versus Nonobese Patients despite Differences in Interstitial Tissue Fluid Pharmacokinetics.Pharmaceutics · 2021Article
- Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Nonparametric goodness-of-fit testing for parametric covariate models in pharmacometric analyses.CPT: pharmacometrics & systems pharmacology · 2021Article
- Towards a Quantitative Mechanistic Understanding of Localized Pulmonary Tissue Retention-A Combined In Vivo/In Silico Approach Based on Four Model Drugs.Pharmaceutics · 2020Article
- Development and Evaluation of Physiologically Based Pharmacokinetic Drug-Disease Models for Predicting Rifampicin Exposure in Tuberculosis and Cirrhosis Populations.Pharmaceutics · 2019Article
- Automated proper lumping for simplification of linear physiologically based pharmacokinetic systems.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Towards a Generic Tool for Prediction of Meropenem Systemic and Infection-Site Exposure: A Physiologically Based Pharmacokinetic Model for Adult Patients with Pneumonia.Drugs in R&D · 2019Article
- Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope.Toxicology research · 2019Article
- MPBPK-TMDD models for mAbs: alternative models, comparison, and identifiability issues.Journal of pharmacokinetics and pharmacodynamics · 2018Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In drug discovery and development, classical compartment models and physiologically based pharmacokinetic (PBPK) models are successfully used to analyze and predict the pharmacokinetics of drugs. So far, however, both approaches are used exclusively or in parallel, with little to no cross-fertilization. An approach that directly links classical compartment and PBPK models is highly desirable. We derived a new mechanistic lumping approach for reducing the complexity of PBPK models and establishing a direct link to classical compartment models. The proposed method has several advantages over existing methods: Perfusion and permeability rate limited models can be lumped; the lumped model allows for predicting the original organ concentrations; and the volume of distribution at steady state is preserved by the lumping method. To inform classical compartmental model development, we introduced the concept of a minimal lumped model that allows for prediction of the venous plasma concentration with as few compartments as possible. The minimal lumped parameter values may serve as initial values for any subsequent parameter estimation process. Applying our lumping method to 25 diverse drugs, we identified characteristic features of lumped models for moderate-to-strong bases, weak bases and acids. We observed that for acids with high protein binding, the lumped model comprised only a single compartment. The proposed lumping approach established for the first time a direct derivation of simple compartment models from PBPK models and enables a mechanistic interpretation of classical compartment models.
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Registered trials
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.