ArticlePharmaceutical research2012
Novel in vitro-in vivo extrapolation (IVIVE) method to predict hepatic organ clearance in rat.
Article in Pharmaceutical research, 2012. 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, 63 citations in OpenAlex.
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- RAID: Regression Analysis-Based Inductive DNA Microarray for Precise Read-Across.Frontiers in pharmacology · 2022Article
- Recent developments inDrug metabolism reviews · 2021Article
- Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization.Journal of medicinal chemistry · 2021Review
- Evaluation of Pharmacokinetic Drug-Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches.Metabolites · 2021Review
- A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies.Frontiers in cell and developmental biology · 2021Review
- Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling.Pharmaceutics · 2019Review
- Drug Disposition Classification Systems in Discovery and Development: A Comparative Review of the BDDCS, ECCS and ECCCS Concepts.Pharmaceutical research · 2016Review
- Rate-Determining and Rate-Limiting Steps in the Clearance and Excretion of a Potent and Selective p21-Activated Kinase Inhibitor: A Case Study of Rapid Hepatic Uptake and Slow Elimination in Rat.Drug metabolism letters · 2016Article
- Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofTechnology · 2015Article
- ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans.Clinical pharmacology and therapeutics · 2013Review
- An overview of the evidence and mechanisms of herb-drug interactions.Frontiers in pharmacology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDrug elimination in the liver consists of uptake, metabolism, biliary excretion, and sinusoidal efflux from the hepatocytes to the blood. We aimed to establish an accurate prediction method for liver clearance in rats, considering these four elimination processes. In vitro assays were combined to achieve improved predictions.
methodsIn vitro clearances for uptake, metabolism, biliary excretion and sinusoidal efflux were determined for 13 selected compounds with various physicochemical and pharmacokinetic properties. Suspended hepatocytes, liver microsomes and sandwich-cultured hepatocytes were evaluated as in vitro models. Based on the individual processes, in vivo hepatic clearance was calculated. Subsequently, the predicted clearances were compared with the corresponding in vivo values from literature.
resultsUsing this in vitro-in vivo extrapolation method good linear correlation was observed between predicted and reported clearances. Linear regression analysis revealed much improved prediction for the novel method (r(2) = 0.928) as compared to parameter analysis using hepatocyte uptake only (r(2) = 0.600), microsomal metabolism only (r(2) = 0.687) or overall hepatobiliary excretion in sandwich-cultured hepatocytes (r(2) = 0.321).
conclusionsIn this new attempt to predict hepatic elimination under consideration of multiple clearance processes, in vivo hepatic clearances of 13 compounds in rats were well predicted using an IVIVE analysis method based on in vitro assays.
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