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

Stephen C. Piscitelli*, Susan Vogel, William D. Figg, Sangeeta Raje, Alan Forrest, Julia A. Metcalf, Michael Baseler, Judith Falloon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 I 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.

Original languageEnglish
Pages (from-to)1212-1216
Number of pages5
Issue number6 I
StatePublished - Nov 1998


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