title: Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents.
  
  
  METHODS
  Phase I, nonrandomized, open-label study in two stages.
  
  
  METHODS
  Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200 mg twice daily) combination antiretroviral regimen.
  
  
  RESULTS
  Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses.
  
  
  CONCLUSIONS
  Etravirine 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. ckoenigs@zki.uni-frankfurt.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Königs
authors.forename: Cornelia
authors.initials: C
authors.lastname: Feiterna-Sperling
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rosso
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Ruud
authors.initials: R
authors.lastname: Leemans
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mack
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Peeters
authors.forename: Rekha
authors.initials: R
authors.lastname: Sinha
authors.forename: Katia
authors.initials: K
authors.lastname: Boven
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage; D008297:Male; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D019438:Ritonavir / Q000008:administration & dosage; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; C451734:etravirine; D061466:Lopinavir; D019438:Ritonavir