Physical model approach to gastrointestinal absorption of prostaglandins II: In situ rat intestinal absorption of dinoprost.
In situ absorption studies with dinoprost in the rat jejunum were carried out using a modified Doluisio technique. The absorption rate was first order. There was a sigmoidal decrease in the rate with increasing buffer pH (from 3.5 to 9.5), which strongly indicated the partitioning of weak acid species into the lipoidal membrane. An asymptotic minimum rate was attained from buffer pH 7.5 to 9.5, operationally indicative of transport of anions across aqueous pores. The importance of the aqueous diffusion layer on the mucosal side of the membrane was evident; rates at pH 3.5 and 4.5 were faster at high agitation hydrodynamics in the lumen solution. Preliminary studies showed that there was no metabolism in the lumenal solution and that metabolism occurred within the membrane. The transport mechanism involved simultaneous passive diffusion and bioconversion in the membrane because (a) a 1.5 X 10(4)-fold range in dinoprost concentration (0.014-210 microM) showed no saturable carrier-mediated tendency on the rate, (b) iodoacetic acid and indomethacin did not inhibit the absorption rate, and (c) the shape of the absorption-pH profiles was suggestive of passive diffusion. The prostaglandin did not have apparent adverse membrane and vascular effects under the conditions employed. The quantification and factorization of the physically meaningful transport parameters were accomplished using the physical model previously described. The permeability coefficients of the aqueous diffusion layer for the oscillation and static hydrodynamic situations were 0.8 X 10(-4) and 1.7 X 10(-4) cm/s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002855:Chromatography, Thin Layer / Q000379:methods; D015237:Dinoprost; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010539:Permeability; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011460:Prostaglandins F; D015237:Dinoprost