Pharmacokinetics and pharmacodynamics of subcutaneous interleukin-2 in HIV-infected patients.
OBJECTIVE
To assess the pharmacokinetics and pharmacodynamics of subcutaneously administered interleukin-2 (IL-2) in patients infected with the human immunodeficiency virus (HIV).


METHODS
Open, dose-escalating phase I clinical trial.


METHODS
Government research hospital.


METHODS
Eighteen patients infected with HIV.


METHODS
Recombinant IL-2 at dosages of 12, 15, or 18 MIU/day was administered subcutaneously once or twice/day for 5 consecutive days every 2 months. A total of 28 cycles of therapy were included in the analysis.


RESULTS
Concentrations of IL-2 in serum were determined by a commercial enzyme-linked immunosorbent assay. Interleukin-2 was well absorbed, with peak concentrations from 21.9-112.9 IU/ml. Absorption was slow, with mean (+/- SD) time to maximum of 4.4 +/- 1.8 hours and a lag time of 26.9 +/- 13.7 minutes. Elimination half-life was 3.3 +/- 0.9 hours. The concentrations had wide variability both within and among patients. Levels of tumor necrosis factor-alpha were increased. Maximum body temperature and systemic side effects were associated with peak serum levels.


CONCLUSIONS
Interleukin-2 is well absorbed after subcutaneous injection in HIV-infected patients, and that route of administration is an alternative to intravenous infusions.
Piscitelli
S C
SC
Department of Pharmacy, Warren G. Magnuson Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. spisc@nih.gov
Wells
M J
MJ
Metcalf
J A
JA
Baseler
M
M
Stevens
R
R
Davey
R T
RT
D000328:Adult; D019540:Area Under Curve; D005260:Female; D005334:Fever / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha