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 onecompartment 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.