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

Induction and drug development.

D A Smith1

  • 1Department of Drug Metabolism, Pfizer Central Research, Kent CT13 9NJ, Sandwich, UK.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|October 24, 2000
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

AACE medical guidelines for clinical practice for the diagnosis and treatment of dyslipidemia and prevention of atherogenesis.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·2001
Same author

Female meadow voles housed in long and short daylengths respond to exogenous estrogen with similar mating latencies.

Physiology & behavior·2001
Same author

Going global with osteopathic medicine.

The Journal of the American Osteopathic Association·2001
Same author

Hemispheric specialization in emotion: attention, arousal, and EEG activation in unilateral temporal lobe epilepsy.

The International journal of neuroscience·2001
Same author

Smads mediate signaling of the TGFbeta superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis.

Oncogene·2001
Same author

Property-based design: optimization of drug absorption and pharmacokinetics.

Journal of medicinal chemistry·2001
Same journal

Innovative Peptide Formulations for Cardiovascular Diseases Using Supercritical CO<sub>2</sub>: A Comprehensive Review and Potential Applications.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
Same journal

An injectable nanoreinforced hydrogel for combined GDNF-loaded nanoparticles and mesenchymal stem cell therapy in Parkinson's disease.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
Same journal

Lipid nanoparticles for Cas9 ribonucleoprotein delivery: design and evaluation of ionisable oligoamine-lipidoids.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
Same journal

Synthesis and Biological Evaluation of Novel Carbazole Derivatives as Broad-Spectrum Antibacterial Agents to Fight Antimicrobial Resistance (AMR).

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
Same journal

Rheological Modeling and Torque-Based Processability Prediction for Celecoxib/PVPVA Hot-Melt Extruded Amorphous Solid Dispersions.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
Same journal

Design, synthesis, and biological analysis of aurein 1.2 analogues incorporating fluorinated phenylalanine.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2026
See all related articles

Enzyme induction, a drug interaction affecting efficacy, is often dose-dependent. High doses of drugs can induce cytochrome P450 enzymes like CYP3A4, while more potent drugs at lower doses may avoid this interaction.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Medicinal Chemistry

Background:

  • Enzyme induction is an undesirable drug interaction that impacts co-administered drug efficacy, not safety.
  • While many drugs have induction potential pre-clinically, this rarely translates to clinical situations.
  • Current screening methods using human hepatocytes are limited by supply and response variability.

Purpose of the Study:

  • To explore the factors influencing clinical enzyme induction, particularly cytochrome P450 (CYP) induction.
  • To investigate the relationship between drug dose, potency, and the potential for enzyme induction.
  • To provide guidance for drug discovery and development programs to mitigate enzyme induction risks.

Main Methods:

  • Analysis of clinical data on known enzyme inducers and non-inducers.

Related Experiment Videos

  • Review of pre-clinical screening data and limitations.
  • Examination of drug properties, including lipophilicity (LogP) and dose size.
  • Case study comparison of troglitzone and rosiglitazone.

    • Main Results:

    • The major inducible cytochrome P450 enzyme in humans is CYP3A4.
    • Clinically significant CYP3A4 induction is primarily associated with drugs administered at high daily doses.
    • Lower doses of more potent drugs, like rosiglitazone, can avoid CYP3A4 induction seen with less potent analogues like troglitzone.
    • Lipophilicity is a general characteristic of enzyme inducers, but no specific structure-activity relationships are evident from clinical data.

    Conclusions:

    • Drug dose size is a critical factor in clinical enzyme induction, especially for CYP3A4.
    • Adhering to "Golden Rules" of drug design, focusing on moderate daily dose size and target potency, can minimize enzyme induction.
    • Optimizing pharmacokinetics and potency allows for lower therapeutic doses, reducing the risk of undesirable drug interactions.