The transmucosal absorption of recombinant human interferon-alpha B/D hybrid in the rat and rabbit.
For therapeutic proteins such as interferon-alpha B/D, a non-parenteral route of delivery is desirable. Possible sites of administration include the various regions of the gastrointestinal tract and airways, and this paper reports the bioavailability of interferon-alpha B/D via these routes in the rat and rabbit. Apart from the stomach, detectable levels of interferon-alpha B/D in the serum were achieved via all routes. Bioavailabilities were less than 1%, except from the lung (6.8% in the rat) and nasal cavity (2.9% in the rabbit). Absorption from the gastrointestinal tract was similar for both species, but in the nasal cavity of the rabbit was sixfold that of the rat, and in the lung of the rat was tenfold that in the rabbit. Absorption from all routes, except the buccal cavity, resulted in detectable biochemical changes in the liver of the rabbit. Comparison with reports from other groups show differences in the extent of absorption of interferon-alpha B/D and of natural or homologous recombinant interferon-alpha. The non-parenteral delivery of biochemically active amounts of interferon-alpha B/D is thus demonstrated.
Bayley
D
D
Ciba Pharmaceuticals, Horsham, West Sussex, UK.
Temple
C
C
Clay
V
V
Steward
A
A
Lowther
N
N
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004064:Digestive System / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016898:Interferon-alpha; D008168:Lung / Q000378:metabolism; D008297:Male; D064547:Myxovirus Resistance Proteins; D009296:Nasal Cavity / Q000378:metabolism; D011506:Proteins / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014132:Trachea / Q000378:metabolism
D007370:Interferon Type I; D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C080665:interferon-alpha A-D; D019204:GTP-Binding Proteins