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Prediction of Human Pharmacokinetics From Preclinical Information: Comparative Accuracy of Quantitative Prediction Approaches
TLDR
Use of predictive methods involving either single‐species in vivo data or in vitro human liver microsomes can quantitatively predict human in vivo pharmacokinetics are suggested and the possibility of streamlining the predictive methodology through use of a single species or use only of human in vitro microsomal preparations is suggested.
Mechanistic Pharmacokinetic Modeling for the Prediction of Transporter-Mediated Disposition in Humans from Sandwich Culture Human Hepatocyte Data
TLDR
This study illustrates the mechanistic and model-driven application of in vitro uptake and efflux data for human PK prediction for OATP substrates and shows the ability to capture the multiphasic plasma concentration-time profiles for such compounds using only preclinical data.
A Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics
TLDR
PBPK can guide experimental efforts to obtain the relevant information necessary to understand the compound’s properties before entry into human, ultimately resulting in a higher level of prediction accuracy.
SUBSTRATE DEPLETION APPROACH FOR DETERMINING IN VITRO METABOLIC CLEARANCE: TIME DEPENDENCIES IN HEPATOCYTE AND MICROSOMAL INCUBATIONS
TLDR
It is recommended that low enzyme concentrations and short incubation times are used whenever possible when using the substrate depletion approach for in vivo CLint and CLH, based on the results obtained for this class of drugs.
PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: prediction of plasma concentration-time profiles in human by using the physiologically-based pharmacokinetic modeling
TLDR
The PBPK approach based on in vitro-input data was as accurate as the approachbased on in vivo data and the implications of compound properties are demonstrated.
The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: computer-based simulation (SimCYP™) predicts in vivo metabolic inhibition
TLDR
Prediction of clinically important drug-drug interaction with SimCYP™ using in vitro human metabolism data can be a powerful tool during early clinical development to ensure safe administration of anticancer drugs, which are often co-administered at maximum tolerated doses with other drugs as part of a palliative treatment regimen.
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 2: comparative assessment of prediction methods of human volume of distribution.
TLDR
Evaluated methodologies for the prediction of human volume of distribution at steady state with and without protein binding corrections found the top three methods that perform strongly at integrating in vivo data in this way were the Øie-Tozer, the rat -dog-human proportionality equation, and the lumped-PBPK approach.
Maraviroc: in vitro assessment of drug-drug interaction potential.
TLDR
Simcyptrade mark has successfully simulated the extent of clinical interactions with CYP3A4 inhibitors, further validating this software as a good predictor of CYP-based DDIs.
Simulation of Human Intravenous and Oral Pharmacokinetics of 21 Diverse Compounds Using Physiologically Based Pharmacokinetic Modelling
TLDR
The utility of PBPK methodology for the prediction of human pharmacokinetics can be applied at different stages to enhance the understanding of the compounds in a particular chemical series, guide experiments, aid candidate selection and inform clinical trial design.
In Vitro Evaluation of Hepatic Transporter-Mediated Clinical Drug-Drug Interactions: Hepatocyte Model Optimization and Retrospective Investigation
TLDR
The in vitro active uptake value could serve as a cutoff for class 3 and 4 compounds of the Biopharmaceutics Drug Disposition Classification System, which could be integrated into the International Transporter Consortium decision tree recommendations to trigger clinical evaluations for potential DDI risks.
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