ArticlePharmaceutical research2005
Prediction of human drug clearance from in vitro and preclinical data using physiologically based and empirical approaches.
Article in Pharmaceutical research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 255 citations in OpenAlex.
- Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels.Clinical pharmacokinetics · 2016Trial
- Impact of Preclinical Verification in Physiologically Based Pharmacokinetic Modelling for First-in-Human Predictions: Application of a Published Model Building Strategy for Five Compounds.Clinical pharmacokinetics · 2026Article
- Machine learning-based unified models for predicting drug clearance from pharmacokinetic animal and study design variables.PloS one · 2026Article
- Elucidating the Phase I metabolism of psilocin in vitro.Archives of toxicology · 2025Article
- Pre-ADMET studies of 5-(3',4'-dihydroxyphenyl)-γ-valerolactone, the bioactive intestinal metabolite of proanthocyanidins.Archiv der Pharmazie · 2025Article
- Predicting Clearance with Simple and Permeability-Limited Physiologically Based Pharmacokinetic Frameworks: Comparison of Well-Stirred, Dispersion, and Parallel-Tube Liver Models.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- 2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors ofJournal of medicinal chemistry · 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
- Current Approaches for Predicting Human PK for Small Molecule Development Candidates: Findings from the IQ Human PK Prediction Working Group Survey.The AAPS journal · 2022Review
- Recent developments inDrug metabolism reviews · 2021Article
- Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization.Journal of medicinal chemistry · 2021Review
- Beyond the Michaelis-Menten: Accurate Prediction of In Vivo Hepatic Clearance for Drugs With Low KClinical and translational science · 2020Article
- In Vitro Toxicokinetics and Phase I Biotransformation of the Mycotoxin Penitrem A in Dogs.Toxins · 2020Article
- The Segregated Intestinal Flow Model (SFM) for Drug Absorption and Drug Metabolism: Implications on Intestinal and Liver Metabolism and Drug-Drug Interactions.Pharmaceutics · 2020Review
- Biotransformation of the Mycotoxin Enniatin B1 by CYP P450 3A4 and Potential for Drug-Drug Interactions.Metabolites · 2019Article
- Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling.Pharmaceutics · 2019Review
- In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from HumanizedDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
- Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs.Molecules (Basel, Switzerland) · 2018Article
- An examination of protein binding and protein-facilitated uptake relating to in vitro-in vivo extrapolation.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study is to compare the accuracy of five methods for predicting in vivo intrinsic clearance (CL(int)) and seven for predicting hepatic clearance (CL(h)) in humans using in vitro microsomal data and/or preclinical animal data.
methodsThe human CL(int) was predicted for 33 drugs by five methods that used either in vitro data with a physiologic scaling factor (SF), with an empirical SF, with the physiologic and drug-specific (the ratio of in vivo and in vitro CL(int) in rats) SFs, or rat CL(int) directly and with allometric scaling. Using the estimated CL(int), the CL(h) in humans was calculated according to the well-stirred liver model. The CL(h) was also predicted using additional two methods: using direct allometric scaling or drug-specific SF and allometry.
resultsUsing in vitro human microsomal data with a physiologic SF resulted in consistent underestimation of both CL(int) and CL(h). This bias was reduced by using either an empirical SF, a drug-specific SF, or allometry. However, for allometry, there was a substantial decrease in precision. For drug-specific SF, bias was less reduced, precision was similar to an empirical SF. Both CL(int) and CL(h) were best predicted using in vitro human microsomal data with empirical SF. Use of larger data set of 52 drugs with the well-stirred liver model resulted in a best-fit empirical SF that is 9-fold increase on the physiologic SF.
conclusionsOverall, the empirical SF method and the drug-specific SF method appear to be the best methods; they show lower bias than the physiologic SF and better precision than allometric approaches. The use of in vitro human microsomal data with an empirical SF may be preferable, as it does not require extra information from a preclinical study.
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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.