PHARMACOKINETIC STUDY OF PARTIALLY PURE GAMMA-INTERFERON IN CANCER-PATIENTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 4164-4171
Abstract
A pharmacokinetic study was performed with partially pure immune (.gamma.) interferon (IFN-.gamma.) in patients with metastatic cancer. Nine patients were given IFN-.gamma. by the i.m. route in doses ranging from 1.5 .times. 105-9.6 .times. 106 antiviral units. There was no detectable antiviral activity in patients'' serum and only minimal side effects were observed. Patients (15) were given IFN-.gamma. by i.v. bolus infusion in doses ranging from 1.5 .times. 105-54 .times. 106 units. Serum clearance of antiviral activity was described by a monoexponential disappearance curve. The serum half-life was dose dependent (3 min at the lower doses and 34 min at the highest doses). There were few consistent biological effects observed in the patients. Based on these pharmacokinetic data, 8 patients were treated by a 6-h continuous infusion consisting of 3 .times. 106 units by i.v. bolus followed by 4 .times. 106 units/h for 6 h. This regimen resulted in consistent serum levels of IFN-.gamma. ranging from 40-60 U over the 6-h period. Marked granulocytopenia occurred within 24 h and was sustained during the 10-day infusion period. There was marked increase in serum .beta.2-microglobulin. In order to induce consistent serum antiviral activity, partially pure IFN-.gamma., because of its rapid serum disappearance curve, must be administered by continuous i.v. infusion.