title: MDR-1 genotypes and quetiapine pharmacokinetics in healthy volunteers.
abstract: BACKGROUND
  P-glycoprotein is an efflux transporter encoded by the multidrug-resistance MDR-1 gene, which influences the absorption and excretion of a variety of drugs. The relation between quetiapine pharmacokinetics and MDR-1 genetic polymorphisms remains controversial. Therefore, the aim of the present study was to analyze the association between quetiapine plasma concentrations and MDR-1 genetic polymorphisms in a bioequivalence trial.
  
  
  METHODS
  Quetiapine bioequivalence was studied in 24 unrelated healthy Caucasian adults with an open-label, randomized, cross-over, two-sequence and two-period design. Subjects were genotyped for 3435C>T and 1236C>T single-nucleotide polymorphisms. A linear mixed model was performed to compare pharmacokinetic parameters.
  
  
  RESULTS
  Subjects with 3435T/T genotype vs. C carriers showed a higher area under the concentration-time curve from 0 to 36 h (p=0.01). Subjects classified according to 1236C>T SNP and haplotypes showed no statistically significant differences.
  
  
  CONCLUSIONS
  These results suggest that the polymorphic MDR-1, in particular the 3435C>T allelic variant, might influence plasma levels of quetiapine.
authors.forename: Nicolás
authors.initials: N
authors.lastname: González-Vacarezza
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Eva M
authors.initials: EM
authors.lastname: Peñas-Lledó
authors.forename: Humberto
authors.initials: H
authors.lastname: Fariñas
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Estévez-Carrizo
authors.forename: Adrián
authors.initials: A
authors.lastname: Llerena
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D003987:Dibenzothiazepines / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000069348:Quetiapine Fumarate
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate