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 duodenum.
The effect of sodium lauryl sulfate (CAS 151-21-3) on the duodenal absorption of cefadroxil (CAS 50370-12-2) has been investigated with the aid of a classical rat gut in situ preparation. Both compounds were entirely compatible in working solutions. Cefadroxil was found to be very stable and only slightly solubilized in the micellar phase. The apparent first-order absorption rate constants for the free antibiotic fraction were determined in free solution, and in the presence of variable surfactant concentration in luminal fluid. A functional interpretation of these data, based both on the law of mass action and the complete noncompetitive transport inhibition equations, showed that the surfactant acts as a nonspecific inhibitor of the carrier-mediated absorption of the antibiotic, but also as an enhancer of its passive absorption component. The net result was an outstanding reduction in the absorption capacity of cefadroxil when it was perfused at 0.1 mg/ml, i.e. far from its carrier saturation (from 3.0 h-1 in free solution to 2.0(-1) at high surfactant concentration, with a minimum of about 1.4 h-1 in the presence of the surfactant at 0.5 mg/mg in duodenal fluid). When cefadroxil was perfused at 10.0 mg/ml, i.e. with its carrier-mediated transport beyond the saturation, the net result was a progressively enhanced absorption (ranging from about 0.9 h-1 in free solution to 2.0 h-1 at high surfactant concentration).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001702:Biopharmaceutics; D002434:Cefadroxil / Q000737:chemistry / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000737:chemistry / Q000493:pharmacokinetics*; D004344:Drug Incompatibility; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D008823:Micelles; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
D002511:Cephalosporins; D008823:Micelles; D013501:Surface-Active Agents; D002434:Cefadroxil; D012967:Sodium Dodecyl Sulfate