Alteration in Indinavir Clearance During Interleukin‐2 Infusions in Patients Infected with the Human Immunodeficiency Virus

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.