Genotype and phenotype relationship in drug metabolism.
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. Today, the relationships between dosage requirements and genetic variations in drug-metabolizing enzymes such as cytochrome P450 (CYP) 2D6, CYP2C9, and CYP2C19 or in drug transporters such as p-glycoprotein (ABCB1) and OATP-C (SLC21A6) are 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 because of higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. In some cases, genetic tests can help distinguish between responders and nonresponders of a specific drug treatment, and genotype-based dosage is possible.
Roots
I
I
Institut für Klinische Pharmakologie, Charité, Universitätsmedizin Berlin, Germany. ivar.roots@charite.de
Laschinski
G
G
Arjomand-Nahad
F
F
Kirchheiner
J
J
Schwarz
D
D
Brockmöller
J
J
Cascorbi
I
I
Gerloff
T
T
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004345:Drug Industry / Q000379:methods*; D004967:Estrogens / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D010601:Pharmacology, Clinical; D010641:Phenotype; D011110:Polymorphism, Genetic; D058831:Serotonin 5-HT3 Receptor Antagonists
D004967:Estrogens; D058831:Serotonin 5-HT3 Receptor Antagonists; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019363:Cytochrome P-450 CYP1A1; D065731:Cytochrome P-450 CYP2C19