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The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.
TLDR
The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to defined a data package that can be expected by regulatory agencies in compound registration dossiers.
The Conduct of in Vitro Studies to Address Time-Dependent Inhibition of Drug-Metabolizing Enzymes: A Perspective of the Pharmaceutical Research and Manufacturers of America
TLDR
A team of scientists from 16 pharmaceutical research organizations that are member companies of the Pharmaceutical Research and Manufacturers of America offer a discussion of the phenomenon of TDI with emphasis on the laboratory methods used in its measurement.
The Conduct of In Vitro and In Vivo Drug‐Drug Interaction Studies: A PhRMA Perspective
TLDR
The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug‐drug interaction studies targeted to development (not discovery support) and to defined a data package that can be expected by regulatory agencies in compound registration dossiers.
Absorption, Metabolism, and Excretion of [14C]Vildagliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, in Humans
TLDR
The diverse metabolic pathways combined with a lack of significant P450 metabolism make vildagliptin less susceptible to potential pharmacokinetic interactions with comedications of P450 inhibitors/inducers.
Comparison of different approaches to predict metabolic drug-drug interactions.
  • H. Einolf
  • Chemistry, Medicine
    Xenobiotica; the fate of foreign compounds in…
  • 1 October 2007
TLDR
Overall, the MDM approach showed an improvement in the prediction of DDI magnitude compared to the other methods evaluated and was useful in its ability to predict variability in D DI magnitude and pharmacokinetic parameters.
Cytochrome P450 1A2 Detoxicates Aristolochic Acid in the Mouse
TLDR
It is reported here that CYP1A2-deficient mice display increased sensitivity to the nephrotoxic effects of AAI, and Cyp1a2 knockout mice accumulate AAI-derived DNA adducts in the kidney at a higher rate than control mice.
Evaluation of Calibration Curve–Based Approaches to Predict Clinical Inducers and Noninducers of CYP3A4 with Plated Human Hepatocytes
TLDR
This study supports the use of calibration curves generated from in vitro mRNA induction response curves to predict CYP3A4 induction potential in human by demonstrating a strong and predictive relationship between the extent of midazolam AUC change in humans and the various parameters calculated from both CYP 3A4 mRNA and enzyme activity.
Evaluation of Various Static and Dynamic Modeling Methods to Predict Clinical CYP3A Induction Using In Vitro CYP3A4 mRNA Induction Data
TLDR
Several drug–drug interaction (DDI) prediction models were evaluated for their ability to identify drugs with cytochrome P450 (CYP)3A induction liability based on in vitro mRNA data and resulted in DDI predictions with less accuracy.
Physiologically Based Pharmacokinetic Model Qualification and Reporting Procedures for Regulatory Submissions: A Consortium Perspective
This work provides a perspective on the qualification and verification of physiologically based pharmacokinetic (PBPK) platforms/models intended for regulatory submission based on the collective
Fidelity of Nucleotide Insertion at 8-Oxo-7,8-dihydroguanine by Mammalian DNA Polymerase δ
TLDR
The presence of PCNA was found to be a more essential factor forucleotide incorporation opposite 8-oxoG adducts than unmodified DNA, increased pre-steady-state rates of nucleotide incorporation by >2 orders of magnitude, and was essential for nucleotide extension beyond 8-OxoG.
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