Utility of hepatocytes in predicting drug metabolism: comparison of hepatic intrinsic clearance in rats and humans in vivo and in vitro.

No abstract is available for this paper.

• Publication year

  2003

• Venue

  Drug Metabolism And Disposition

• Publication date

  2003-05-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1124/DMD.31.5.580PMID 12695346
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Therapeutic doses of codeine have no effect on acetaminophen clearance or metabolism

  2004cited by this paper
• Studies comparing in vivo:in vitro metabolism of three pharmaceutical compounds in rat, dog, monkey, and human using cryopreserved hepatocytes, microsomes, and collagen gel immobilized hepatocyte cultures.

  2001cited by this paper
• Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans.

  2001influential reference
• Survival and function of isolated hepatocytes after cryopreservation.

  1999cited by this paper
• Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man.

  1999influential reference
• Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential.

  1999cited by this paper
• Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes.

  1999cited by this paper
• In vivo clearance of ethoxycoumarin and its prediction from In vitro systems. Use Of drug depletion and metabolite formation methods in hepatic microsomes and isolated hepatocytes.

  1998cited by this paper
• Correlating Partitioning and Caco-2 Cell Permeability of Structurally Diverse Small Molecular Weight Compounds

  1998cited by this paper
• Metabolic activity of fresh and cryopreserved dog hepatocyte suspensions.

  1998cited by this paper
• Linear Correlation of the Fraction of Oral Dose Absorbed of 64 Drugs Between Humans and Rats

  1998cited by this paper
• Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices.

  1997cited by this paper
• Cytochrome-P450 induction and conjugated metabolism in primary human hepatocytes after cryopreservation

  1997influential reference
• Integration of in vitro data into allometric scaling to predict hepatic metabolic clearance in man: application to 10 extensively metabolized drugs.

  1997cited by this paper
• Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data.

  1997cited by this paper
• Design principles for orally bioavailable drugs

  1996cited by this paper
• Estimation of oral drug absorption in man based on intestine permeability in rats.

  1996cited by this paper
• PREDICTION OF IN VIVO DRUG DISPOSITION FROM IN VITRO DATA BASED ON PHYSIOLOGICAL PHARMACOKINETICS

  1996cited by this paper
• Prediction of the human pharmacokinetics of troglitazone, a new and extensively metabolized antidiabetic agent, after oral administration, with an animal scale-up approach.

  1996cited by this paper
• Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam.

  1996cited by this paper
• Prediction of in vivo disposition from in vitro systems: clearance of phenytoin and tolbutamide using rat hepatic microsomal and hepatocyte data.

  1995cited by this paper
• Pharmacokinetics and metabolism of diltiazem in rats following a single intra-arterial or single oral dose

  1994cited by this paper
• Predicting the hepatic clearance of xenobiotics in humans from in vitro data

  1994cited by this paper
• Physiological Parameters in Laboratory Animals and Humans

  1993influential reference
• The protein binding of quinotolast to the serum and plasma and its distribution in the blood cells

  1993cited by this paper
• Viability and function in primary culture of adult hepatocytes from various animal species and human beings after cryopreservation

  1993cited by this paper
• Cryopreservation of human adult hepatocytes for use in drug metabolism and toxicity studies.

  1993cited by this paper
• Pharmacokinetics of quinotolast sodium in rats, guinea pigs and dogs

  1993cited by this paper
• Na(+)-independent multispecific anion transporter mediates active transport of pravastatin into rat liver.

  1993cited by this paper
• Pharmacokinetics of diazepam in the rat: influence of a carbon tetrachloride-induced hepatic injury.

  1992cited by this paper
• Decreased Systemic Clearance of Diltiazem with Increased Hepatic Metabolism in Rats with Uranyl Nitrate-Induced Acute Renal Failure

  1992cited by this paper
• A nonprimate animal model applicable to zidovudine pharmacokinetics in humans: inhibition of glucuronidation and renal excretion of zidovudine by probenecid in rats.

  1991cited by this paper
• Tissue distribution and metabolic disposition of zidovudine in rats.

  1990cited by this paper
• Probenecid Inhibits the Metabolic and Renal Clearances of Zidovudine (AZT) in Human Volunteers

  1990cited by this paper
• Clinical Pharmacokinetics of Zidovudine

  1989cited by this paper
• Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis.

  1988cited by this paper
• Pharmacokinetics and bioavailability of zidovudine in humans.

  1988cited by this paper
• Effect of prevention of inorganic sulfate depletion on the pharmacokinetics of acetaminophen in rats.

  1986cited by this paper
• Correlation between in‐vitro microsomal enzyme activity and whole organ hepatic elimination kinetics: analysis with a dispersion model

  1986influential reference
• Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats

  1985cited by this paper
• Glucuronidation and biliary excretion of acetaminophen in rats.

  1984cited by this paper
• Pharmacokinetic model of diltiazem.

  1983cited by this paper
• Pharmacokinetic model of diltiazem.

  1983cited by this paper
• Pharmacokinetics of diltiazem in selected animal species and human beings.

  1982cited by this paper
• Kinetic studies on the deethylation of ethoxybenzamide. A comparative study with isolated hepatocytes and liver microsomes of rat.

  1980cited by this paper
• Biochemical studies on liver functions in primary cultured hepatocytes of adult rats. III. Changes of enzyme activities on cell membranes during culture.

  1979cited by this paper
• Biochemical studies on liver functions in primary cultured hepatocytes of adult rats. I. Hormonal effects on cell viability and protein synthesis.

  1978cited by this paper
• Biochemical studies on liver functions in primary cultured hepatocytes of adult rats. I. Hormonal effects on cell viability and protein synthesis.

  1978cited by this paper
• Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance

  1977cited by this paper
• Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat.

  1976cited by this paper
• The binding of paracetamol to plasma proteins of man and pig

  1973cited by this paper
• [Pharmacokinetics of N-acetyl-para-aminophenol under the effect of phenylbutazone].

  1970cited by this paper

• Characterizing the Hepatic Metabolic Pathway of Ketone Ester and Subsequent Metabolites Using Human and Rat Liver Fractions

  2025influential citation
• Contribution of Japanese scientists to drug metabolism and disposition.

  2025cites this paper
• Advancing hepatotoxicity assessment: current advances and future directions

  2025cites this paper
• Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

  2024cites this paper
• Establishing a physiologically based pharmacokinetic framework for aldehyde oxidase and dual aldehyde oxidase‐CYP substrates

  2024cites this paper
• Identification of PPA1 inhibitor candidates for potential repurposing in cancer medicine

  2023cites this paper
• In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes

  2023cites this paper
• Challenges and Opportunities for In Vitro–In Vivo Extrapolation of Aldehyde Oxidase-Mediated Clearance: Toward a Roadmap for Quantitative Translation

  2023influential citation
• Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies

  2023cites this paper
• Investigation of pharmacokinetic properties of a PEGylated bilirubin nanoparticle in male Sprague-Dawley rats using liquid chromatography-quadrupole time-of-flight mass spectrometry

  2023influential citation
• Application of a Volumetric Absorptive Microsampling (VAMS)-Based Method for the Determination of Paracetamol and Four of its Metabolites as a Tool for Pharmacokinetic Studies in Obese and Non-Obese Patients.

  2022cites this paper
• The evaluation of ADME and pharmacokinetic properties of decoquinate derivatives for the treatment of malaria

  2022cites this paper
• High-throughput PBTK models for in vitro to in vivo extrapolation

  2021cites this paper
• Prediction of Hepatic Drug Clearance with a Human Microfluidic Four-Cell Liver Acinus MicroPhysiology System.

  2021cites this paper
• Ethambutol disposition in humans: challenges and limitations of whole-body physiologically-based pharmacokinetic modelling in early drug development.

  2020cites this paper
• Human plasma concentration-time profiles of troglitazone and troglitazone sulfate simulated by in vivo experiments with chimeric mice with humanized livers and semi-physiological pharmacokinetic modeling.

  2020cites this paper
• Comparative assessment for rat strain differences in metabolic profiles of 14 drugs in Wistar Han and Sprague Dawley hepatocytes

  2020cites this paper
• Using Chemical Structure Information to Develop Predictive Models for In Vitro Toxicokinetic Parameters to Inform High-throughput Risk-assessment.

  2020cites this paper
• Seeking Nonspecific Binding: Assessing the Reliability of Tissue Dilutions for Calculating Fraction Unbound

  2020cites this paper
• Prediction of Atorvastatin Pharmacokinetics in High-Fat Diet and Low-Dose Streptozotocin-Induced Diabetic Rats Using a Semiphysiologically Based Pharmacokinetic Model Involving Both Enzymes and Transporters

  2019cites this paper
• A Comparison of Total and Plasma Membrane Abundance of Transporters in Suspended, Plated, Sandwich-Cultured Human Hepatocytes Versus Human Liver Tissue Using Quantitative Targeted Proteomics and Cell Surface Biotinylation

  2019cites this paper
• Interlaboratory Variability in Human Hepatocyte Intrinsic Clearance Values and Trends with Physicochemical Properties

  2019cites this paper
• Utility of Chimeric Mice with Humanized Liver for Predicting Human Pharmacokinetics in Drug Discovery: Comparison with in Vitro-in Vivo Extrapolation and Allometric Scaling.

  2019cites this paper
• Species differences in metabolism of a new antiepileptic drug candidate, DSP‐0565 [2‐(2′‐fluoro[1,1′‐biphenyl]‐2‐yl)acetamide]

  2019cites this paper
• Synthesis of new 5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine derivatives with rigidized tryptamine moiety as potential SSRI and 5-HT1A receptor ligands.

  2019cites this paper
• Quantitative Prediction of Human Hepatic Clearance for P450 and Non-P450 Substrates from In Vivo Monkey Pharmacokinetics Study and In Vitro Metabolic Stability Tests Using Hepatocytes

  2019cites this paper
• Use of Segregated Hepatocyte Scaling Factors and Cross-Species Relationships to Resolve Clearance Dependence in the Prediction of Human Hepatic Clearance

  2019cites this paper
• In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction.

  2019cites this paper
• Using the concordance of in vitro and in vivo data to evaluate extrapolation assumptions

  2019cites this paper
• Mathematical modelling of a liver hollow fibre bioreactor.

  2019cites this paper
• Improvements for the in Vitro to in Vivo Extrapolation of Hepatic Clearance

  2019cites this paper
• Metabolic Stability of D-Allulose in Biorelevant Media and Hepatocytes: Comparison with Fructose and Erythritol

  2019cites this paper
• Utility of in vitro clearance in primary hepatocyte model for prediction of in vivo hepatic clearance of psychopharmacons

  2018influential citation
• Prediction of Human Liver Toxicity Using In Vitro Assays: Limitations and Opportunities

  2018cites this paper
• Bioactive Indanes: Comparative in vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and Biosynthesis of its Primary Metabolite PH132

  2018cites this paper
• Clearance in Drug Design.

  2018cites this paper
• In vitro-to-in vivo extrapolation (IVIVE) by PBTK modeling for animal-free risk assessment approaches of potential endocrine-disrupting compounds

  2018cites this paper
• Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors.

  2018cites this paper
• Use of segregated hepatocyte scaling factors and cross-species relationship to resolve clearance-dependency in prediction of human hepatic clearance

  2018cites this paper
• An Intuitive Approach for Predicting Potential Human Health Risk with the Tox21 10k Library.

  2017cites this paper
• Recent Progress in Hepatocyte Culture Models and Their Application to the Assessment of Drug Metabolism, Transport, and Toxicity in Drug Discovery: The Value of Tissue Engineering for the Successful Development of a Microphysiological System.

  2017cites this paper
• Estimation of Interindividual Variability of Pharmacokinetics of CYP2C9 Substrates in Humans.

  2017cites this paper
• Online monitoring of hepatic rat metabolism by coupling a liver biochip and a mass spectrometer.

  2017cites this paper
• 3D engineered In vitro hepatospheroids for studying drug toxicity and metabolism.

  2017cites this paper
• Prediction of inter-individual variability on the pharmacokinetics of CYP2C8 substrates in human.

  2017cites this paper
• Unusual gastrointestinal and cutaneous toxicities by bleomycin, etoposide, and cisplatin: a case report with pharmacogenetic analysis to personalize treatment

  2017cites this paper
• Evaluation and calibration of high-throughput predictions of chemical distribution to tissues

  2017cites this paper
• httk: R Package for High-Throughput Toxicokinetics.

  2017cites this paper
• Clearance Prediction Methodology Needs Fundamental Improvement: Trends Common to Rat and Human Hepatocytes/Microsomes and Implications for Experimental Methodology

  2017cites this paper
• Lead Identification/Optimization

  2017cites this paper
• A Pharmacokinetic Modeling Approach to Predict the Contribution of Active Metabolites to Human Efficacious Dose

  2016cites this paper
• The Use of In Vitro Data and Physiologically-Based Pharmacokinetic Modeling to Predict Drug Metabolite Exposure: Desipramine Exposure in Cytochrome P4502D6 Extensive and Poor Metabolizers Following Administration of Imipramine

  2016influential citation
• Hepatic Clearance Prediction of Nine Human Immunodeficiency Virus Protease Inhibitors in Rat.

  2016cites this paper
• Physiologically based modeling of the pharmacokinetics of acetaminophen and its major metabolites in humans using a Bayesian population approach

  2016cites this paper
• Computational modeling of the pharmacokinetics and pharmacodynamics of selected xenobiotics

  2016cites this paper
• Virtual Experiments Enable Exploring and Challenging Explanatory Mechanisms of Immune-Mediated P450 Down-Regulation

  2016cites this paper
• Intracellular unbound drug concentrations : methodology and application for understanding cellular drug exposure

  2016cites this paper
• Methodology and application for understanding cellular drug exposure

  2016cites this paper
• Prediction of inter-individual variability on the pharmacokinetics of CYP1A2 substrates in non-smoking healthy volunteers.

  2016cites this paper
• Metabolism of six CYP probe substrates in fetal hepatocytes

  2016cites this paper
• Spheroid culture of primary hepatocytes with short fibers as a predictable in vitro model for drug screening.

  2016cites this paper
• Validation of Early Human Dose Prediction: A Key Metric for Compound Progression in Drug Discovery.

  2016cites this paper
• Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics

  2016cites this paper
• Optimisation of in vitro methodology for drug metabolism studies to improve prediction of hepatic drug clearance

  2016influential citation
• International of Advanced Research in Biological Sciences Drug Discovery and ADMET process: A Review

  2016cites this paper
• Optimizing DMPK Properties: Experiences from a Big Pharma DMPK Department.

  2016cites this paper
• Toxicokinetic Triage for Environmental Chemicals.

  2015cites this paper
• The Role of Extrahepatic Metabolism in the Pharmacokinetics of the Targeted Covalent Inhibitors Afatinib, Ibrutinib, and Neratinib

  2015cites this paper
• To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics

  2015cites this paper
• Quantifying and Communicating Uncertainty in Preclinical Human Dose-Prediction

  2015cites this paper
• Prediction of Drug Disposition in Diabetic Patients by Means of a Physiologically Based Pharmacokinetic Model

  2015cites this paper
• A High Throughput, 384-Well, Semi-Automated, Hepatocyte Intrinsic Clearance Assay for Screening New Molecular Entities in Drug Discovery.

  2015cites this paper
• Hepatocyte spheroid culture on fibrous scaffolds with grafted functional ligands as an in vitro model for predicting drug metabolism and hepatotoxicity.

  2015cites this paper
• How to Choose In Vitro Systems to Predict In Vivo Drug Clearance: A System Pharmacology Perspective

  2015cites this paper
• Evaluation of simple in vitro to in vivo extrapolation approaches for environmental compounds.

  2014cites this paper
• Toward modular biological models: defining analog modules based on referent physiological mechanisms

  2014cites this paper
• Identification of human cytochrome P450 isozymes responsible for the in-vitro oxidative demethylation of 4-methylaminoantipyrine

  2014cites this paper
• The role of drug metabolizing enzymes in clearance

  2014cites this paper
• Prediction of inter-individual variability in the pharmacokinetics of CYP2C19 substrates in humans.

  2014cites this paper
• First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating ADME processes in humans

  2014influential citation
• Species variation in the enantioselective metabolism of tegafur to 5‐fluorouracil among rats, dogs and monkeys

  2014cites this paper
• Utility of cryopreserved hepatocytes suspended in serum to predict hepatic clearance in dogs and monkeys.

  2014cites this paper
• Metabolic Stability Assessed by Liver Microsomes and Hepatocytes

  2014cites this paper
• Pharmacokinetic Evaluation of a Novel Benzopyridooxathiazepine Derivative as a Potential Anticancer Agent

  2014cites this paper
• Evaluation of a liver microfluidic biochip to predict in vivo clearances of seven drugs in rats.

  2014cites this paper
• Hepatocyte composition-based model as a mechanistic tool for predicting the cell suspension: aqueous phase partition coefficient of drugs in in vitro metabolic studies.

  2013cites this paper
• Systems toxicology from genes to organs.

  2013cites this paper
• The utility of cold-preserved human hepatocytes in studies on cytochrome P450 induction and hepatic drug transport

  2013cites this paper
• In vitro pharmacokinetic profile of a benzopyridooxathiazepine derivative using rat microsomes and hepatocytes: identification of phases I and II metabolites.

  2013cites this paper
• Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

  2013cites this paper
• Hepatocyte clearance and pharmacokinetics of recombinant factor IX glycosylation variants.

  2013cites this paper
• Development of a hybrid physiologically based pharmacokinetic model with drug-specific scaling factors in rat to improve prediction of human pharmacokinetics.

  2013cites this paper
• Prediction of dose-hepatotoxic response in humans based on toxicokinetic/toxicodynamic modeling with or without in vivo data: a case study with acetaminophen.

  2013influential citation
• Computational Toxicology

  2013cites this paper
• In vitro to in vivo extrapolation and physiologically based modeling of cytochrome P450 mediated metabolism in beagle dog gut wall and liver.

  2013cites this paper
• EFFECT OF OBESITY ON HEPATIC DRUG METABOLISM

  2013cites this paper
• Toward a new paradigm for the efficient in vitro-in vivo extrapolation of metabolic clearance in humans from hepatocyte data.

  2013cites this paper
• Modeling Phospholipidosis Induction: Reliability and Warnings

  2013cites this paper
• Application of in silico, in vitro and preclinical pharmacokinetic data for the effective and efficient prediction of human pharmacokinetics.

  2013cites this paper
• Scaling and systems biology for integrating multiple organs-on-a-chip.

  2013cites this paper