Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency virus

Pharmacotherapy. Nov-Dec 1998;18(6):1212-6.

Abstract

Study objective: To evaluate the effect of interleukin-2 (IL-2) infusions on the pharmacokinetics of indinavir in patients infected with the human immunodeficiency virus.

Design: Observational, noncontrolled trial and prospective, open-label, nonrandomized, pharmacokinetic study.

Setting: Government research hospital.

Patients: Seventeen patients receiving indinavir 800 mg every 8 hours and a 5-day continuous infusion of recombinant IL-2.

Interventions: Observational study: trough indinavir concentrations were measured on day 1 and day 5 of IL-2 as part of a clinical trial. Prospective study: serial plasma samples were collected on days 1 and 5 of IL-2 to determine indinavir concentrations. Samples were also collected over the study period to determine IL-6 concentrations. The data were fit by a one-compartment model that allowed clearance to change based on IL-6 production and by standard noncompartmental equations.

Measurements and main results: The area under the curve of indinavir increased in eight of nine patients by a mean of 88% (range -29-215%) between days 1 and 5 of IL-2 infusion. Over this period, IL-6 concentrations also increased in all patients and indinavir clearance significantly decreased. Observational data in eight patients from the clinical trial showed significantly increased indinavir trough concentrations from 264+/-493 to 670+/-677 ng/ml in the presence of IL-2.

Conclusion: Indinavir concentrations were altered during IL-2 infusions, possibly by induction of IL-6. Investigation into the effects of other proinflammatory cytokines is warranted.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Area Under Curve
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Indinavir / blood
  • Indinavir / pharmacokinetics*
  • Indinavir / therapeutic use
  • Infusions, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Interleukin-6 / blood
  • Male
  • Middle Aged

Substances

  • Anti-HIV Agents
  • Interleukin-2
  • Interleukin-6
  • Indinavir