title: Pharmacokinetics of enfuvirtide in pediatric human immunodeficiency virus 1-infected patients receiving combination therapy.
abstract: BACKGROUND
  Enfuvirtide is the first of a new class of antiretroviral agents, the fusion inhibitors.
  
  
  OBJECTIVE
  The primary objective of this analysis was to evaluate the pharmacokinetics of 2.0 mg/kg enfuvirtide in human immunodeficiency virus 1 (HIV-1)-infected children and adolescents when administered in combination with at least 3 other antiretrovirals.
  
  
  METHODS
  Twenty-five HIV-1-infected pediatric patients (5-16 years of age) enrolled in an ongoing phase I/II study were included in this analysis. Patients received enfuvirtide 2.0 mg/kg sc twice daily (bid) for at least 7 days. Blood samples were collected on day 7, and plasma concentrations of enfuvirtide and its metabolite were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetics measures [Cmax, tmax, Ctrough, and area under the concentration time curve time 0 to 12 hours (AUC12 hours)] were calculated from plasma concentration-time data by standard noncompartmental methods.
  
  
  RESULTS
  There was no significant difference between children and adolescents for enfuvirtide Cmax (6.43 versus 5.88 microg/mL), Ctrough (2.87 versus 2.98 microg/mL) and AUC12 hours (56.1 versus 52.7 hours . microg/mL). Similarly no significant differences were found when the pharmacokinetic measures were compared based on sexual maturity stages. A post hoc regression analysis based on AUC12 hours showed that body weight-adjusted dosing of enfuvirtide provides drug exposure that is independent of age group, body weight and body surface area.
  
  
  CONCLUSIONS
  Body weight-adjusted dosing of enfuvirtide, at a dose of 2.0 mg/kg sc bid, in HIV-1-infected pediatric patients at least 5 years of age, provides drug exposure comparable with that previously observed in HIV-1-infected adults after 90 mg sc bid dosing. Drug exposure in children and adolescents is independent of age group, body weight, body surface area and sexual maturity stage.
authors.affiliation: Roche, Nutley, NJ 07110, USA. eralp.bellibas@roche.com
authors.forename: S Eralp
authors.initials: SE
authors.lastname: Bellibas
authors.forename: Zikia
authors.initials: Z
authors.lastname: Siddique
authors.forename: Albert
authors.initials: A
authors.lastname: Dorr
authors.forename: Anne
authors.initials: A
authors.lastname: Bertasso
authors.forename: Prakash
authors.initials: P
authors.lastname: Sista
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Kolis
authors.forename: Stanley
authors.initials: S
authors.lastname: Cotler
authors.forename: Patricia
authors.initials: P
authors.lastname: Delora
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019540:Area Under Curve; D002648:Child; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage; D023581:HIV Fusion Inhibitors / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide