Estimation of sieving coefficients of convective absorption of drugs in perfused rat jejunum.
Intestinal absorption of many hydrophilic drugs cannot be explained solely in terms of pH-partition and solvent-drag effects have been described in a number of cases. However, quantitative estimates of sieving coefficient (phi) for drug molecules have tended to be variable. In the present work an in situ perfused intestinal loop preparation in the rat has been used to measure the disappearance of five hydrophilic drugs from the intestinal lumen and a mathematical model of drug absorption in the presence of net and unidirectional fluid fluxes has been developed. The model allows separate estimation of the convective (solvent drag) and nonconvective (partition) components of drug absorption from the experimental data. The five drugs studied were found to have phi values ranging from 0.1-0.9; this was highly dependent on molecular size. Analysis of the data shows that three of the drugs are absorbed almost exclusively by the convective process (caffeine, cimetidine, hydrochlorthiazide) while the other two are absorbed by both convective and nonconvective processes (salicylate, oxprenolol). We conclude that the methodology is a useful and reliable means of deriving separate estimates of these two components of drug absorption.
Leahy
D E
DE
ZENECA Pharmaceuticals, Mereside, Cheshire, United Kingdom.
Lynch
J
J
Finney
R E
RE
Taylor
D C
DC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007408:Intestinal Absorption / Q000502:physiology; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D051381:Rats