[Therapeutic implications of polymorphisms in cytochromes and drug transporters].
There is great heterogeneity in the way individuals respond to drug therapy. Reasons for this variability include pathophysiological or environmental factors, drug interactions or genetic influences. Among those influences are polymorphisms in drug-metabolizing enzymes, such as Cytochrom-P-450 (CYP) 2D6, CYP2C9 or CYP2C19 or genetic variants in enzymes coding for drug transporters, such as P-Glycoprotein. Polymorphisms might cause changes in drug pharmacokinetics and consequently drug efficacy after administration of recommended standard drug doses. Reduced enzyme activity can either result in a higher percentage of drug side-effects, or an augmented drug response due to increased target site concentrations. Conversely, intensified catalytic enzymatic activity might lead to subtherapeutic drug concentrations. In the future, genetic screening by genotyping before the initiation of pharmacotherapy might help to identify responders or non-responders and might it offer individualized therapies to select patient populations.
Münster
Eva
E
Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien, Wien, Osterreich.
Ziegler
Sophie
S
Brunner
Martin
M
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D018579:Patient Selection; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System