ReviewThe AAPS journal2009
Prediction of hepatic clearance in human from in vitro data for successful drug development.
Review in The AAPS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
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Who cites it
74 citing papers in PubMed.
- Development and Validation of an LC-MS/MS Method for the Quantitation of JNJ-64619178 (JNJ) in Mouse Plasma: Characterization of In Vitro and In Vivo Pharmacokinetic Properties.Molecules (Basel, Switzerland) · 2026Article
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- Beyond the Michaelis-Menten: Evaluation of a tQSSA-Based IVIVE Approach for Predicting In Vivo Intrinsic Clearance From Hepatocyte Assays.CPT: pharmacometrics & systems pharmacology · 2026Article
- Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Simultaneous estimation of finerenone and canagliflozin using HPLC: application in metabolic stability studies.Bioanalysis · 2025Article
- Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity.Journal of medicinal chemistry · 2025Article
- Application of Kirchhoff's Laws to pharmacologic and pharmacokinetic analyses.Pharmacological reviews · 2025Review
- Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor withbioRxiv : the preprint server for biology · 2025Article
- Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates.Beilstein journal of organic chemistry · 2025Article
- In Vitro Hepatic Metabolism Input Parameters Support Toxicokinetic Simulations for the Formation of Methoxy Propionic Acid From β-Isomer Propylene Glycol Methyl Ether.Pharmacology research & perspectives · 2024Article
- Commentary: Pharmacokinetic Theory Must Consider Published Experimental Data.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Liver-on-chips for drug discovery and development.Materials today. Bio · 2024Review
- Data set of fraction unbound values in the in vitro incubations for metabolic studies for better prediction of human clearance.Database : the journal of biological databases and curation · 2024Article
- Conquering the beyond Rule of Five Space with an Optimized High-Throughput Caco-2 Assay to Close Gaps in Absorption Prediction.Pharmaceutics · 2024Article
- Uridine 5'-Diphospho-glucuronosyltransferase 1A3 (UGT1A3) Prediction of Hepatic Clearance of Organic Anion Transporting Polypeptide 1B3 (OATP1B3) Substrate Telmisartan by Glucuronidation Using In Vitro-In Vivo Extrapolation (IVIVE).European journal of drug metabolism and pharmacokinetics · 2024Article
- Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- EvaluatingFrontiers in pharmacology · 2024Review
- HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.Journal of medicinal chemistry · 2023Article
- Metabolic stability and metabolite profiling of emerging synthetic cathinones.Frontiers in pharmacology · 2023Article
- Characterization of a Potential KOR/DOR Dual Agonist with No Apparent Abuse Liability via a Complementary Structure-Activity Relationship Study on Nalfurafine Analogues.ACS chemical neuroscience · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The in vivo metabolic clearance in human has been successfully predicted by using in vitro data of metabolic stability in cryopreserved preparations of human hepatocytes. In the predictions by human hepatocytes, the systematic underpredictions of in vivo clearance have been commonly observed among different datasets. The regression-based scaling factor for the in vitro-to-in vivo extrapolation has mitigated discrepancy between in vitro prediction and in vivo observation. In addition to the elimination by metabolic degradation, the important roles of transporter-mediated hepatic uptake and canalicular excretion have been increasingly recognized as a rate-determining step in the hepatic clearance. It has been, therefore, proposed that the in vitro assessment should allow the evaluation of clearances for both transporter(s)-mediated uptake/excretion and metabolic degradation. This review first outlines the limited ability of subcellular fractions such as liver microsomes to predict hepatic clearance in vivo. It highlights the advantages of cryopreserved human hepatocytes as one of the versatile in vitro systems for the prediction of in vivo metabolic clearance in human at the early development stage. The following section discusses the mechanisms underlying the systematic underprediction of in vivo intrinsic clearance by hepatocytes. It leads to the proposal for the assessment of hepatic uptake clearance as one of the kinetically important determinants for accurate predictions of hepatic clearance in human. The judicious combination of advanced technologies and understandings for the drug disposition allows us to rationally optimize new chemical entities to the drug candidate with higher probability of success during the clinical development.
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