Small intestinal absorption of bropirimine in rats and effect of bile salt on the absorption.
The intestinal absorption characteristics of a poorly water-soluble drug, bropirimine, were investigated by the in-situ small intestinal loop method using male Sprague-Dawley rats. Bropirimine in solution was well absorbed in the overall small intestine, following first-order kinetics. The rate determining step for the disappearance of bropirimine from the small intestinal loop after dosing in the suspension was the dissolution process from suspension. Bropirimine was solubilized by sodium glycocholate. The disappearance of bropirimine from the small intestinal loop was suppressed by sodium glycocholate contained in the solution, because of the loss of thermodynamic activity of bropirimine after its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa. The disappearance of bropirimine was also suppressed by sodium glycocholate contained in the suspension. The suppression by sodium glycocholate seemed to be caused by the greater influence of sodium glycocholate on the thermodynamic activity of bropirimine than on the dissolution from suspension.
Emori
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H
Upjohn Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Ibaraki, Japan.
Yokohama
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Nishihata
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T
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003864:Depression, Chemical; D006000:Glycocholic Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013500:Surface Tension; D013816:Thermodynamics
D000276:Adjuvants, Immunologic; D003596:Cytosine; D006000:Glycocholic Acid; C033560:bropirimine