THE LYMPHATIC ROUTE .9. DISTRIBUTION OF RECOMBINANT INTERFERON-ALPHA(2) ADMINISTERED SUBCUTANEOUSLY WITH OEDEMATOGENIC DRUGS

We have evaluated whether the addition of either bradykinin or histami ne favours the lymphatic adsorption of human recombinant interferon-al pha2 (IFN-alpha2) administered by the subcutaneous route. Subcutaneous administration of IFN-alpha2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so that either the plasma or lymp h areas under the concentration curves (AUC) increase significantly up to 1751 +/- 483 and 1319 +/- 608 IU/ml/min respectively as compared t o the respective AUC values (613 +/- 208 and 483 +/- 213 IU/ml/min) ob tained after IFN injection in normal saline. Since the lymph AUC/plasm a AUC ratios remain unaltered, there is no preferential lymphatic abso rption of IFN-alpha2 after bradykinin administration. Dual-label exper iments, I-125-IFN-alpha2 in saline and I-131-IFN-alpha2 in saline cont aining 200 mug histamine were injected subcutaneously into the left an d into the right shank of the same animal, gave similar results. The k inetics of I-125 and I-131 acid-soluble radioactivity confirm that his tamine favours both plasmatic and lymphatic absorption.