title: The influence of the CYP3A4*22 polymorphism on serum concentration of quetiapine in psychiatric patients.
abstract: BACKGROUND
  Besides dietary, hormonal, or pathological factors, mutations in cytochrome P450 enzymes are thought to be responsible for the interindividual differences in serum concentrations of cytochrome P450 (CYP450)-dependent drugs. Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, a new single-nucleotide polymorphism (SNP) was found (CYP3A4*22), which results in a decreased enzyme activity, in contrast to the other known SNPs in CYP3A4. We investigated to which degree the CYP3A4*22 SNP affects serum concentrations of patients receiving quetiapine, a drug exclusively metabolized by CYP3A4.
  
  
  METHODS
  Two hundred thirty-eight adult patients receiving quetiapine were included in this study, based on availability of DNA, serum quetiapine levels, and information on dose. Patients were genotyped for CYP3A4*22 using allele-specific polymerase chain reaction, and, as a control, restriction fragment length polymorphism analysis.
  
  
  RESULTS
  Carriers of the CYP3A4*22 allele (*1/*22 and *22/*22, n = 31) had 2.5-fold higher serum levels of quetiapine than did wild-type patients (n = 207; P = 0.03) when using a comparable dose (median, 300 mg/d for both wild-type and carriers; P = 0.67). The dose-corrected serum concentration (C/D) was 67% higher in carriers than in wild-type patients (P = 0.01). The number of patients who achieved serum levels above the therapeutic range (>500 µg/L) was also higher in *22-allele carriers (16.1% vs 2.9%; P = 0.007).
  
  
  CONCLUSIONS
  Being a carrier of the CYP3A4*22 allele increases the serum concentration of quetiapine at comparable doses.
authors: From the *St Jansdal Hospital, Department of Clinical Chemistry, Harderwijk; and †Psychiatric Hospital GGz Centraal, location Veldwijk, Ermelo, the Netherlands.
authors: Karen
authors: K
authors: van der Weide
authors: Jan
authors: J
authors: van der Weide
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood*; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D003987:Dibenzothiazepines / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human