[Analysis and its application for prevention of side-effects of drugs and for evaluation of drug responsiveness].
The response of patients to drugs can be affected by genetic polymorphisms/defects in drug metabolizing enzymes, transporters, and receptors. Genetic polymorphisms/defects are generated by mutation of coding regions and/or noncoding regions of target genes, such as single-point mutations, deletions/insertions, variation in the number of tandem repeats, etc. If a genetic defect in a patient which affects drug response were known, it would be possible to optimize medications individually. The author developed two improved methods for detecting CYP2C19(*)2 and CYP2C19(*)3. Using the methods, the type of CYP2C19 gene was examined in 80 inpatients, and the medication status of patients with the mutation was examined focusing on dosage and side effects. The author also examined polymorphisms of the serotonin transporter/biosynthetic or metabolizing enzymes in depressive patients treated with fluvoxamine, a selective serotonin reuptake inhibitor, and the relationship between clinical efficacy and polymorphisms was investigated. As a result, patients with the S/S genotype of 5-HTTLPR were found to experience better clinical efficacy.
Inoue
Kazuyuki
K
Department of Pharmaceutical Science, Akita University Hospital, Japan. kazinoue@hos.akita-u.ac.jp
D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use
D001189:Aryl Hydrocarbon Hydroxylases; D002352:Carrier Proteins; D065731:Cytochrome P-450 CYP2C19; D016666:Fluvoxamine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D006899:Mixed Function Oxygenases; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C045793:CYP2C19 protein, human