Plasma and tissue pharmacokinetics of human interferon-alpha in the rat after its intravenous administration.
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.
Greig
N H
NH
Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland.
Soncrant
T T
TT
Wozniak
K M
KM
Rapoport
S I
SI
D000818:Animals; D006801:Humans; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D007370:Interferon Type I