Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency virus.
OBJECTIVE
To evaluate the effect of interleukin-2 (IL-2) infusions on the pharmacokinetics of indinavir in patients infected with the human immunodeficiency virus.


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


METHODS
Government research hospital.


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


METHODS
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.


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.


CONCLUSIONS
Indinavir concentrations were altered during IL-2 infusions, possibly by induction of IL-6. Investigation into the effects of other proinflammatory cytokines is warranted.
Piscitelli
S C
SC
Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Vogel
S
S
Figg
W D
WD
Raje
S
S
Forrest
A
A
Metcalf
J A
JA
Baseler
M
M
Falloon
J
J
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged
D019380:Anti-HIV Agents; D007376:Interleukin-2; D015850:Interleukin-6; D019469:Indinavir