Colonic absorption of insulin-like growth factor I in vitro.
Colonic absorption of recombinant human insulin-like growth factor I (rhIGF-I) was measured in vitro using both rat and minipig colon. The permeability coefficients were 8.03 +/- 1.03 and 4.75 +/- 0.43 x 10(-8) cm sec-1 in the rat and minipig, respectively. The steady-state flux in rat colon was linearly related to the donor concentration over the range 1 to 10 mg/mL. rhIGF-I was metabolically stable in contact with both mucosal and serosal surfaces of washed colon for 5 hr. The amount of IGF-I permeating through the tissue was quantitated by radioimmunoassay and the identity and integrity of the permeating species were confirmed by reverse-phase HPLC, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting. In all cases the permeant was identical to authentic rhIGF-I. The integrity of the colonic tissue in vitro was demonstrated by the maintenance of electrophysiological parameters, a secretory response to serosal theophylline, and the ability of sodium azide, a metabolic inhibitor, to abolish the barrier properties and cause a large increase in flux.
Quadros
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E
Ciba-Geigy Corporation, Pharmaceutical Division, Ardsley, New York 10502.
Landzert
N M
NM
LeRoy
S
S
Gasparini
F
F
Worosila
G
G
D000818:Animals; D001386:Azides / Q000494:pharmacology; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D019810:Sodium Azide; D013552:Swine; D013556:Swine, Miniature; D013806:Theophylline / Q000494:pharmacology
D001386:Azides; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D019810:Sodium Azide; D013806:Theophylline