Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection

Three groups of six subjects each received a single 36 × 10 6 U dose of recombinant leukocyte A interferon (rIFN‐αA) as a 40‐min infusion, an intramuscular injection, or a subcutaneous injection. Blood samples were collected at specific times after dosing for analysis of rIFN‐αA serum concentrations by an enzyme immunoassay method, ELISA. The rIFN‐αA was rapidly distributed and moderately eliminated (t½ =5.1 hr) after intravenous infusion. The maximum concentrations at the end of intravenous infusion were tenfold the maximum concentrations after intramuscular and subcutaneous injections. Renal tubular secretion or extrarenal elimination was suggested by clearance values of 1.8 times the glomerular filtration rate. After intramuscular and subcutaneous injection, rIFN‐αA was absorbed slowly (time to reach maximum concentration ranged from 4 to 8 hr), which resulted in prolonged serum concentrations. Estimated bioavailability was more than 80% for both intramuscular and subcutaneous injection shares qualitatively the same adverse reactions, the reactions differ in severity and duration. The adverse effects appear to be related to route of administration, of herpes labialis were also noted. There were no significant clinical laboratory abnormalities of medical concern. Although rIFN‐αA injected by intravenous infusion or intramuscular or subcutaneous injection shares qualitatively the same adverse reactions, the reactions differ in severity and duration. The adverse effects appear to be related to route of administration. Clinical Pharmacology and Therapeutics (1984) 35, 722–727; doi: 10.1038/clpt.1984.101