EXPERIMENTAL STUDIES ON THE INFLUENCE OF SURFACTANTS ON INTESTINAL-ABSORPTION OF DRUGS - CEFADROXIL AS MODEL-DRUG AND SODIUM LAURYL SULFATEAS MODEL SURFACTANT - STUDIES IN RAT COLON

The effect of the anionic surfactant, sodium lauryl sulfate (CAS 151-2 1-9), on the absorption of cefadroxil (CAS 50370-12-2) as model antibi otic in colon has been studied by means of an in situ rat gut techniqu e, as a previous step to investigate the influence of the surfactant o n the intestinal, carrier-mediated absorption of the antibiotic. Micro bial degradation tests were initially performed, which demonstrated th at cefadroxil disappearance from luminal content was only due to absor ption. Micelle solubilization of cefadroxil was also previously assess ed through dialysis tests in order to adequately correct absorption ra te constant values found in the presence of the surfactant at supramic ellar concentration. Micelle solubilization was minimal although stati stically significant. Apparent passive absorption rate constants, k(al pha)(h(-1)), were determined in the presence of variable concentration s of lauryl sulfate in perfusion fluids. Results showed that k(alpha) values greatly increased as surfactant luminal concentration increased until an asymptotic value (about 7-fold higher than cefadroxil alone) was obtained; this was assumed to be due to a direct effect of the su rfactant on membrane polarity. Moreover, the results were satisfactori ly adjusted using a functional hyperbolic-type equation, as occurs wit h many other saturable processes. This was supposed to be indicative t hat the surfactant effect is due to an adsorption process of the surfa ctant ions or molecules to the intestinal absorbent membrane.