title: Pharmacokinetic study of the variability of indinavir drug levels when boosted with ritonavir in HIV-infected children.
abstract: The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m(2) IDV yielded trough levels below 0.10 microg/ml (median: 0.21, range: 0.04-1.31 microg/ml). When the dosage was increased to 400 mg/m(2) IDV plus 100 mg/m(2) RTV b.i.d., all, except 1 patient, achieved levels above 0.10 microg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.
authors.affiliation: Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Curras
authors.forename: Christian
authors.initials: C
authors.lastname: Hocht
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.forename: Viviana
authors.initials: V
authors.lastname: Niselman
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mariño Hernández
authors.forename: Paulo
authors.initials: P
authors.lastname: Cáceres Guido
authors.forename: Débora
authors.initials: D
authors.lastname: Mecikovsky
authors.forename: Carolina
authors.initials: C
authors.lastname: Bellusci
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.forename: Modesto C
authors.initials: MC
authors.lastname: Rubio
authors.forename: Guillermo F
authors.initials: GF
authors.lastname: Bramuglia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D002648:Child; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005091:Exons; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D011110:Polymorphism, Genetic; D019438:Ritonavir / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir