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Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency
S C Piscitelli1, S Vogel, W D Figg
1Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
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.