ArticleJournal of pharmacokinetics and pharmacodynamics2002
A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics.
Article in Journal of pharmacokinetics and pharmacodynamics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Hepatic OATP1B zonal distribution: Implications for rifampicin-mediated drug-drug interactions explored within a PBPK framework.CPT: pharmacometrics & systems pharmacology · 2024Article
- A Complete Extension of Classical Hepatic Clearance Models Using Fractional Distribution Parameter fJournal of pharmaceutical sciences · 2024Article
- Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- A multiscale modelling approach to assess the impact of metabolic zonation and microperfusion on the hepatic carbohydrate metabolism.PLoS computational biology · 2018Article
- A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD.PLoS computational biology · 2016Article
- Article
- Drug structure-transport relationships.Journal of pharmacokinetics and pharmacodynamics · 2010Review
- An improved nonlinear model describing the hepatic pharmacokinetics of digoxin: evidence for two functionally different uptake systems and saturable binding.Pharmaceutical research · 2010Article
- Tissue-level modeling of xenobiotic metabolism in liver: An emerging tool for enabling clinical translational research.Clinical and translational science · 2009Article
- Modeling and simulation of hepatic drug disposition using a physiologically based, multi-agent in silico liver.Pharmaceutical research · 2008Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The conventional convection-dispersion model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver bloodflow on F and Cl. The extension of this model to include nonlinear kinetics and zonal heterogeneity of the liver is not straightforward and requires numerical solution of partial differential equation, which is not available in standard nonlinear regression analysis software. In this paper, we describe an alternative compartmental model representation of hepatic disposition (including elimination). The model allows the use of standard software for data analysis and accurately describes the outflow concentration-time profile for a vascular marker after bolus injection into the liver. In an evaluation of a number of different compartmental models, the most accurate model required eight vascular compartments, two of them with back mixing. In addition, the model includes two adjacent secondary vascular compartments to describe the tail section of the concentration-time profile for a reference marker. The model has the added flexibility of being easy to modify to model various enzyme distributions and nonlinear elimination. Model predictions of F, MTT, CV2, and concentration-time profile as well as parameter estimates for experimental data of an eliminated solute (palmitate) are comparable to those for the extended convection-dispersion model.
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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.