Pharmacokinetics of recombinant human interferon-gamma in the rhesus monkey after intravenous, intramuscular, and subcutaneous administration.
The pharmacokinetics of recombinant human interferon-gamma (rIFN-gamma) were studied in rhesus monkeys. Intravenous administration of 0.1 mg/kg yielded half-lives of 12.3-13.4 min and 130 min. Clearance after intravenous administration was 18.7 ml/min/kg, and the steady-state volume of distribution (Vdss) was 510 ml/kg. The peak serum concentrations after intramuscular and subcutaneous administration of 0.25 mg/kg rIFN-gamma were 50.7 and 52.3 ng/ml, respectively. The time to reach the peak serum concentration was 480 min for both routes. The mean bioavailabilities after intramuscular and subcutaneous administration were 109 and 90%, respectively. Intravenous administration of 0.25 mg/kg rIFN-gamma resulted in no significant change in the clearance, half-life, or Vdss, suggesting that the kinetics of rIFN-gamma are linear over the range of doses tested. Nearly all of the animals developed antibodies to rIFN-gamma after three doses. The presence of nonneutralizing antibodies to rIFN-gamma had no discernible effect on the calculated pharmacokinetic parameters.
D000818:Animals; D000917:Antibody Formation; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D008253:Macaca mulatta
D007371:Interferon-gamma