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.
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
S C
SC
Piscitelli
M J
MJ
Wells
J A
JA
Metcalf
M
M
Baseler
R
R
Stevens
R T
RT
Davey
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