Experimental studies on the influence of surfactants on intestinal absorption of drugs. Cefadroxil as model drug and sodium lauryl sulfate as model surfactant: studies in rat colon.
The effect of the anionic surfactant, sodium lauryl sulfate (CAS 151-21-3), on the absorption of cefadroxil (CAS 50370-12-2) as model antibiotic in colon has been studied by means of an in situ rat gut technique, as a previous step to investigate the influence of the surfactant on the intestinal, carrier-mediated absorption of the antibiotic. Microbial degradation tests were initially performed, which demonstrated that cefadroxil disappearance from luminal content was only due to absorption. Micelle solubilization of cefadroxil was also previously assessed through dialysis tests in order to adequately correct absorption rate constant values found in the presence of the surfactant at supramicellar concentration. Micelle solubilization was minimal, although statistically significant. Apparent passive absorption rate constants, ka(h-1), were determined in the presence of variable concentrations of lauryl sulfate in perfusion fluids. Results showed that ka 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 surfactant on membrane polarity. Moreover, the results were satisfactorily adjusted using a functional hyperbolic-type equation, as occurs with many other saturable processes. This was supposed to be indicative that the surfactant effect is due to an adsorption process of the surfactant ions or molecules to the intestinal absorbent membrane.
Sancho-Chust
V
V
Department of Pharmaceutics, University of Valencia, Spain.
Fabra-Campos
S
S
Gómez-Meseguer
V
V
Bengochea
M
M
Martín-Villodre
A
A
D000818:Animals; D001711:Biotransformation; D001834:Body Water / Q000378:metabolism; D002434:Cefadroxil / Q000493:pharmacokinetics*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008823:Micelles; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000494:pharmacology*
D008823:Micelles; D013501:Surface-Active Agents; D002434:Cefadroxil; D012967:Sodium Dodecyl Sulfate