title: ABCB1 polymorphisms and the concentrations of lopinavir and ritonavir in blood, semen and saliva of HIV-infected men under antiretroviral therapy.
abstract: BACKGROUND
  Lopinavir and ritonavir are frequently included in highly active antiretroviral therapy (HAART) regimens for HIV infection. These drugs are substrates, and may also inhibit and/or induce the P-glycoprotein (ABCB1) transporter, encoded by the polymorphic ABCB1 gene. We investigated the impact of three common exonic ABCB1 polymorphisms on the concentrations of lopinavir and ritonavir in blood, semen and saliva of HIV-infected men under stable HAART containing ritonavir-boosted lopinavir.
  
  
  METHODS
  Blood, semen and saliva samples were collected from 113 subjects, 30-35 minutes before the scheduled morning dose of lopinavir/ritonavir, and trough drug concentrations were measured using LC/MS/MS. The 1236C>T, 2677G>T/A and 3435C>T polymorphisms were genotyped using the single base extension-termination method and ABCB1 haplotypes were statistically inferred.
  
  
  RESULTS
  Median (25th-75th percentile) trough concentrations (ng/ml) of lopinavir in plasma, semen and saliva were 6326 (4070-8617), 286.0 (128.4-475.5) and 72.7 (38.0-119.6), respectively. The corresponding concentrations (ng/ml) for ritonavir were 261.8 (172.2-398.6), 17.7 (9.2-27.6) and 5.3 (3.2-9.0), respectively. Univariate and multivariate regression analysis revealed no influence of ABCB1 genotypes or haplotypes on the concentrations of lopinavir and ritonavir in plasma, semen and saliva of HIV-infected men under stable HAART treatment.
  
  
  CONCLUSIONS
  The ABCB1 1236C>T, 2667G>T/A and 3435C>T genotypes and haplotypes are not predictors of lopinavir and ritonavir concentrations in blood plasma, semen or saliva of HIV-infected men under stable HAART treatment. The concentrations of lopinavir and ritonavir in saliva are not reliable predictors of the concentration of these drugs in semen.
authors.affiliation: Divisão de Farmacologia, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro 21230-050, Brazil.
authors.forename: Rita de Cassia
authors.initials: Rde C
authors.lastname: Estrela
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Ribeiro
authors.forename: Paulo F
authors.initials: PF
authors.lastname: Barroso
authors.forename: Mari
authors.initials: M
authors.lastname: Tuyama
authors.forename: Sheila P
authors.initials: SP
authors.lastname: Gregório
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dias-Neto
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Struchiner
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011744:Pyrimidinones / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D012463:Saliva / Q000378:metabolism*; D012661:Semen / Q000378:metabolism*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir