TY - JOUR
T1 - Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency virus
AU - Piscitelli, Stephen C.
AU - Vogel, Susan
AU - Figg, William D.
AU - Raje, Sangeeta
AU - Forrest, Alan
AU - Metcalf, Julia A.
AU - Baseler, Michael
AU - Falloon, Judith
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031726789&partnerID=8YFLogxK
U2 - 10.1002/j.1875-9114.1998.tb03139.x
DO - 10.1002/j.1875-9114.1998.tb03139.x
M3 - Article
C2 - 9855318
AN - SCOPUS:0031726789
SN - 0277-0008
VL - 18
SP - 1212
EP - 1216
JO - Pharmacotherapy
JF - Pharmacotherapy
IS - 6 I
ER -