Abstract
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.
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