title: Changes in indinavir exposure over time: a case study in six HIV-1-infected children.
abstract: OBJECTIVE
  To study changes in indinavir exposure over time in HIV-1-infected children.
  
  
  METHODS
  Protease inhibitor (PI)-naive HIV-1-infected children were treated with indinavir, zidovudine and lamivudine. Steady-state plasma pharmacokinetic (PK) sampling was carried out as standard of care. The AUC(0-8) was targeted between 15 and 30 mg h/L. PK sampling was repeated after dosage adjustment until the AUC(0-8) reached target values. Patients were included when the time interval between PK samplings was > or =2 years and differences in dosage/m2 <10% between PK samplings 1 and 2. Corrections of dose for changes in body size were carried out.
  
  
  RESULTS
  Six children were enrolled with a median age of 5.2 years (range 1.7-13.6 years). All had a viral load below 500 copies/mL. The geometric mean (GM) of the AUC(0-8) decreased from 25.3 mg h/L at the first PK-day to 19.1 mg h/L at the second PK-day [geometric mean ratio (GMR): 0.76 (95% C.I.: 0.48-1.20)]. The GM of Cmax decreased from 11.8 to 10.4 mg/L [GMR: 0.88 (95% C.I.: 0.59-1.32)]. The GM of Cmin decreased from 0.08 to 0.07 mg/L [GMR: 0.86 (95% C.I.: 0.62-1.18)]. All children had an AUC(0-8) above 15 mg h/L on the first PK-day; three had an AUC(0-8) below 15 mg h/L on the second PK-day. In two of these three children, the plasma viral load was >500 copies/mL.
  
  
  CONCLUSIONS
  Changes in indinavir exposure were observed over time. In two patients, decreased indinavir exposure was associated with virological failure. Therapeutic drug monitoring should be carried out over time since this may prevent subtherapeutic dosing in children.
authors.affiliation: Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: P L A
authors.initials: PL
authors.lastname: Fraaij
authors.forename: A S
authors.initials: AS
authors.lastname: Bergshoeff
authors.forename: A M C
authors.initials: AM
authors.lastname: van Rossum
authors.forename: N G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.forename: R
authors.initials: R
authors.lastname: de Groot
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D013997:Time Factors
chemical_list: D019469:Indinavir