Pharmacokinetics, Single-Dose Tolerance, and Biological Activity of Recombinant γ-lnterferon in Cancer Patients

TLDR: Data suggest that further studies with i.v. as well as prolonged i.m. infusions of rlFN-γ are indicated, suggesting partial loss of antiviral activity at the i.V. site.

Abstract: We report a clinical study of the pharmacokinetics, toxicity, and biological activity of iv- and im-administered recombinant γ-interferon (rlFN-γ) consisting of 143 amino acids Ten patients with metastatic cancer were given rlFN-γ at doses of 001 to 25 mg/sq m by alternating im and iv bolus injections with a minimum intervening period of 72 h After iv administration, rlFN-γ was cleared monoexponentially with a short half-life of 25 to 35 min as determined by bioassay and enzyme immunoassay After im injection, a longer half-life of 227 to 462 min was measured by enzyme immunoassay Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the im site However, other biological effects were retained as evidence by fever, chills, and fatigue after both routes of administration and granulocytopenia after im, but not iv, doses Two of ten patients showed objective evidence of tumor regression These data suggest that further studies with im as well as prolonged iv infusions of rlFN-γ are indicated