Pharmacogenetics-based new therapeutic concepts.
Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.
Roots
Ivar
I
Institut für Klinische Pharmakologie, Charité-Universitätsmedizin Berlin, Campus Charitè Mitte, Humboldt-Universität zu Berlin, Berlin, Germany. ivar.roots@charite.de
Gerloff
Thomas
T
Meisel
Christian
C
Kirchheiner
Julia
J
Goldammer
Mark
M
Kaiser
Rolf
R
Laschinski
Gabriele
G
Brockmöller
Jürgen
J
Cascorbi
Ingolf
I
Kleeberg
Ullrich
U
Hildebrandt
Alfred G
AG
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods* / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism
D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System