Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Time-dependent CYP inhibition.

Robert J Riley1, Ken Grime, Richard Weaver

  • 1AstraZeneca R&D Charnwood, Department of Physical and Metabolic Science, Loughborough, Leicestershire LE11 5RH, UK. rob.riley@astrazeneca.com

Expert Opinion on Drug Metabolism & Toxicology
|February 3, 2007
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

In Vitro ADME Profiling of PROTACs: Successes, Challenges, and Lessons Learned from Analysis of Clinical PROTACs from a Diverse Physicochemical Space.

Journal of medicinal chemistry·2025
Same author

Proof of lung muscarinic receptor occupancy by tiotropium: Translational Positron Emission Tomography studies in non-human primates and humans.

Frontiers in nuclear medicine·2024
Same author

Pharmacokinetics of N,N-dimethyltryptamine in Humans.

European journal of drug metabolism and pharmacokinetics·2023
Same author

Epithelial senescence in idiopathic pulmonary fibrosis is propagated by small extracellular vesicles.

Respiratory research·2023
Same author

Studying the right transporter at the right time: an <i>in vitro</i> strategy for assessing drug-drug interaction risk during drug discovery and development.

Expert opinion on drug metabolism & toxicology·2022
Same author

Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs.

Journal of medicinal chemistry·2022
Same journal

The use of natural language processing in predictive toxicology.

Expert opinion on drug metabolism & toxicology·2026
Same journal

An update on beta-lactam-beta-lactamase inhibitor combinations for the treatment of carbapenem-resistant gram-negative pathogens.

Expert opinion on drug metabolism & toxicology·2026
Same journal

Optimizing tamoxifen therapy in breast cancer: a narrative review of dose escalation in patients with CYP2D6 polymorphisms.

Expert opinion on drug metabolism & toxicology·2026
Same journal

Effect of concomitant rifampin and clarithromycin on elexacaftor-tezacaftor-ivacaftor using a physiologically based pharmacokinetic (PBPK) modeling approach.

Expert opinion on drug metabolism & toxicology·2026
Same journal

Gastrointestinal bleeding risk among antithrombotics users: a propensity score matched study of drug classes.

Expert opinion on drug metabolism & toxicology·2026
Same journal

Complex <i>in vitro</i> model developers' perspective on advanced hepatic <i>in vitro</i> culture methods for predictive drug safety.

Expert opinion on drug metabolism & toxicology·2026
See all related articles

Time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes can lead to drug-drug interactions and toxicity. This review highlights TDI

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Toxicology

Background:

  • Cytochrome P450 (CYP) enzymes are crucial for drug metabolism.
  • Time-dependent inhibition (TDI) describes changes in drug potency during incubation or dosing.
  • Mechanisms include inhibitory metabolites and mechanism-based inhibition (MBI).

Purpose of the Study:

  • To review the contribution of CYP TDI to drug-drug interactions.
  • To explore the role of CYP TDI in idiosyncratic drug toxicity.
  • To discuss the challenges in predicting TDI risks compared to reversible inhibition.

Main Methods:

  • Review of existing literature on CYP time-dependent inhibition.
  • Analysis of in vitro experimental approaches to assess TDI and MBI.

Related Experiment Videos

  • Discussion of in vitro-in vivo extrapolation models for TDI.

    • Main Results:

    • MBI effects are more pronounced with multiple dosing and have a recovery period independent of exposure.
    • Advances in modeling competitive inhibition and MBI-toxicity links redirect focus to CYP TDI.
    • Traditional models often underpredict risks associated with TDI.

    Conclusions:

    • CYP TDI is a significant factor in drug-drug interactions and toxicity.
    • Current strategies for predicting TDI risks are less developed than for reversible inhibition.
    • Further research is needed to improve TDI risk assessment and prediction.