ISSN:
1573-2592
Keywords:
Interferon-γ
;
Kaposi's sarcoma
;
human immunodeficiency virus (HIV)
;
pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract A Phase I study of recombinant interferon-gamma (rIFN-γ) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-γ. rIFN-γ was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2–4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7–12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1–1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-γ is given at doses at or near this MTD.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00918667
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