Human recombinant (R) interferon-alpha 2 (either cold or labeled with 125I or 131I) has been administered through different routes [intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.)] and its distribution in lymph and plasma has been evaluated in rabbits and pigs. After i.v. (bolus) administration, the lymph/plasma ratio was about 1. After s.c. and i.m. administration, the ratio varied from an average of 0.8 up to 2, respectively, indicating that R interferon-alpha 2 is preferentially absorbed via lymphatics when injected into the shank muscles. Another novel result is that the ratio is markedly increased after s.c. administration of interferon-alpha 2 with a solution containing 12.5% human albumin. In this case, albumin acts as an interstitial fluid expander, thereby increasing the fluid pressure and favoring lymphatic absorption. Similar results were obtained using either cold or labeled interferons in rabbits; moreover, the effect of albumin was confirmed in the pig by simultaneously injecting 131I-interferon (in saline) and 125I-interferon (in albumin solution) in the left and right subcutis of the shanks, respectively. All of these data suggest that the indirect lymphatic route is a feasible proposition, and that by modifying the absorption, the distribution and fate of interferon may improve the therapeutic index of biological response modifiers.
