PHARMACOKINETICS, SINGLE-DOSE TOLERANCE, AND BIOLOGICAL-ACTIVITY OF RECOMBINANT GAMMA-INTERFERON IN CANCER-PATIENTS

Abstract

A clinical study of the pharmacokinetics, toxicity and biological activity of i.v. and i.m. administered recombinant .gamma.-interferon (rIFN-.gamma.) consisting of 143 amino acids was reported. Ten patients with metastatic cancer were given rIFN-.gamma. at doses of 0.01-2.5 mg/m2 by alternating i.m. and i.v. bolus injections with a minimum intervening period of 72 h. After i.v. administration, rIFN-.gamma. was cleared monooexponentially with a short half-life of 25-35 min as determined by bioassay and enzyme immunoassay. After i.m. injection, a longer half-life of 227-462 min was measured by enzyme immunoassay. Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the i.m. site. Other biological effects were retained as evidenced by fever, chills and fatigue after both routes of administration and granulocytopenia after i.m., but not i.v., doses. Two of 10 patients showed objective evidence of tumor regression. Thus, further studies with i.m. as well as prolonged i.v. infusions of rIFN-.gamma. are indicated.