Plasma and tissue pharmacokinetics of human interferon-alpha in the rat after its intravenous administration

NH Greig, TT Soncrant, KM Wozniak and SI Rapoport

Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland.

The pharmacokinetic distribution of human lymphoblastoid interferon (IFN-alpha), (Wellferon, Burroughs Wellcome Company, Research Triangle Park, NC) in plasma and seven tissues was studied for up to 4 hr after intravascular administration as a bolus, 2 x 10(5) U/100 g, or as a 5- min infusion, 2 x 10(6) U/100 g, into anesthetized male Fischer 344 rats. IFN-alpha disappeared rapidly from plasma with elimination T 1/2 of 47 and 68 min, respectively, and was preferentially taken up by the kidney as compared with other organs. After i.v. injection, significant amounts of IFN-alpha, in order of descending concentration, were detected in kidney, lung, spleen, liver and lymph node, but not in brain or skeletal muscle. After a 5-min IFN-alpha infusion, significant amounts, in order of descending priority, were detected in kidney, lung, spleen, lymph node, liver, muscle and brain. The pharmacokinetic parameters of IFN-alpha are described for plasma and different tissues. After intravascular IFN-alpha administration, high blood levels are achieved immediately which encourages rapid distribution throughout body tissues, albeit at the cost of a high renal catabolic loss, in concentrations that can be predicted from our study.

Volume 245, Issue 2, pp. 574-580, 05/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics