Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection

Clin Pharmacol Ther. 1998 Nov;64(5):492-8. doi: 10.1016/S0009-9236(98)90132-1.


A novel model was developed to characterize the time-varying clearance of recombinant interleukin-2 (IL-2). Sixty-eight patients with human immunodeficiency virus infection received 83 cycles of IL-2 either by continuous infusion or by subcutaneous injection for 5 days. IL-2 concentrations after intravenous infusions peaked at 24 hours and then declined by 55% to 78% during the remainder of the infusion. Soluble IL-2 receptors increased greater than 10-fold before gradually returning to baseline. Subcutaneous administration showed a dose-dependent decrease in area under the concentration-time curve (AUC) between days 1 and 5. A model was developed in 9 patients who had IL-2 concentrations and soluble IL-2 receptors determined by ELISA. Concentrations were fitted by an indirect stimulatory pharmacodynamic model. An additional 59 patients with only IL-2 concentrations were fitted to a simplified empiric model. Both models provided an overall r2 of 0.99 for the plot of observed versus fitted concentrations. The time-dependent increase in IL-2 clearance, likely receptor-mediated, was well described with use of an indirect-effects pharmacokinetic-pharmacodynamic model.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / metabolism*
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacokinetics*
  • Male
  • Middle Aged
  • Models, Theoretical
  • Receptors, Interleukin-2 / metabolism
  • Time Factors


  • Interleukin-2
  • Receptors, Interleukin-2