Population pharmacokinetics of enfuvirtide in pediatric patients with human immunodeficiency virus: searching for exposure-response relationships

Clin Pharmacol Ther. 2003 Dec;74(6):569-80. doi: 10.1016/j.clpt.2003.09.002.


Objective: Our objective was to describe the population pharmacokinetics and pharmacodynamics of enfuvirtide acting on viral ribonucleic acid in children with human immunodeficiency virus 1.

Methods: A 1-compartment population pharmacokinetic model with first-order absorption and elimination was fit to subcutaneous and intravenous dose pharmacokinetic data from a 2-part study, as follows: an intensive-sample pharmacokinetic design (observed dose) (subcutaneous and intravenous, n = 12) followed by a sparse-sample design (unobserved dose) (subcutaneous, n = 15). The parameters of this model are clearance (CL), volume of distribution (V), absorption rate (k(a)), bioavailability (F), and both interindividual and residual variability. Plasma ribonucleic acid concentrations over time were used to build a population viral pharmacodynamics model with the following parameters: viral clearance (CL(v)), initial viral concentration (A(0)), duration (tau) and rate (R) of preinfected cell-based viral input after enfuvirtide was begun, and interindividual and residual variability.

Results: The mean population CL and V of enfuvirtide for a child with a mean body weight of 21.3 kg were 1.42 L/h and 5.67 L, respectively. Patient weight affected CL and V. Volume appeared to differ between intensive and sparse sampling occasions, and this difference also affected the residual error variance. Time after the beginning of therapy did not significantly affect any pharmacokinetic parameter, supporting the absence of metabolic induction and inhibition. Although trends were present, no statistically significant relationship was seen between any pharmacokinetic-based individual enfuvirtide exposure measure and any virologic response measure.

Conclusions: Regarding pharmacokinetics and pharmacodynamics, no statistically significant correlation between exposure measures and viral clearance was observed.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Area Under Curve
  • Bayes Theorem
  • Biological Availability
  • Child
  • Child, Preschool
  • Enfuvirtide
  • Female
  • HIV Envelope Protein gp41 / pharmacology
  • HIV Fusion Inhibitors / pharmacokinetics*
  • HIV Fusion Inhibitors / pharmacology
  • HIV Seropositivity / drug therapy
  • HIV Seropositivity / metabolism*
  • HIV-1*
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Metabolic Clearance Rate
  • Peptide Fragments / pharmacokinetics*
  • Peptide Fragments / pharmacology
  • Viral Load


  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Peptide Fragments
  • Enfuvirtide