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

Clinical consequences of polymorphic drug oxidation.

G Alván1

  • 1Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.

Fundamental & Clinical Pharmacology
|January 1, 1991
PubMed
Summary

Genetic variations in drug metabolism, specifically polymorphic drug oxidation, influence how individuals process medications. While generally part of natural variability, understanding a patient's metabolic phenotype can aid drug dosing for certain treatments.

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

Quantitative pharmacogenetics of nortriptyline: a novel approach.

Clinical pharmacokinetics·2001
Same author

Moving toward genetic profiling in patient care: the scope and rationale of pharmacogenetic/ecogenetic investigation.

Drug metabolism and disposition: the biological fate of chemicals·2001
Same author

Pharmacokinetics and comparative effects of telithromycin (HMR 3647) and clarithromycin on the oropharyngeal and intestinal microflora.

The Journal of antimicrobial chemotherapy·2000
Same author

Lack of polymorphism of the conversion of losartan to its active metabolite E-3174 in extensive and poor metabolizers of debrisoquine (cytochrome P450 2D6) and mephenytoin (cytochrome P450 2C19).

European journal of clinical pharmacology·1999
Same author

The efficiency concept in pharmacodynamics.

Clinical pharmacokinetics·1999
Same author

[Quinine/quinidine treatment of cramps of the calf is not supported by the Pharmaceutical Product Agency].

Lakartidningen·1999

Area of Science:

  • Pharmacogenetics
  • Drug Metabolism
  • Biochemistry

Background:

  • Genetic polymorphisms significantly influence drug metabolism, affecting drug clearance and therapeutic outcomes.
  • Acetylation and oxidation are key polymorphic drug metabolic pathways, with debrisoquine/sparteine and s-mephenytoin hydroxylation being well-established examples.
  • The metabolism of numerous drugs, including beta-blockers, antiarrhythmics, and antidepressants, is linked to the debrisoquine polymorphism.

Purpose of the Study:

  • To review the established polymorphisms in drug oxidation, focusing on the debrisoquine/sparteine and s-mephenytoin hydroxylation pathways.
  • To discuss the clinical implications of polymorphic drug metabolism, including variability in drug clearance and potential for adverse events.
  • To evaluate the practical value of knowing a patient's metabolic phenotype for drug dose adjustments, particularly for drugs with narrow therapeutic indices.

Related Experiment Videos

Main Methods:

  • Review of existing literature on drug metabolism polymorphisms.
  • Analysis of the cytochrome P-450 isozyme responsible for debrisoquine hydroxylation.
  • Examination of drug classes whose metabolism is affected by debrisoquine polymorphism.

Main Results:

  • The debrisoquine/sparteine polymorphism affects the metabolism of several important drug classes, leading to potential accumulation or reduced formation of active metabolites.
  • The cytochrome P-450 isozyme involved exhibits high-affinity, low-capacity kinetics, susceptible to saturation and inhibition.
  • Clinical consequences of polymorphic drug oxidation appear limited for many conditions, but can be significant for drugs like tricyclic antidepressants and neuroleptics.

Conclusions:

  • Polymorphic drug metabolism contributes to inter-individual variability in drug response.
  • Knowledge of a patient's debrisoquine metabolic phenotype may be valuable for optimizing drug dosages, especially for medications with a narrow therapeutic range.
  • Further research is warranted to fully elucidate the clinical significance of drug metabolism polymorphisms for a wider range of drugs and patient populations.