Intestinal absorption mechanism of amphoteric beta-lactam antibiotics I: Comparative absorption and evidence for saturable transport of amino-beta-lactam antibiotics by in situ rat small intestine.

The disappearance of various beta-lactam antibiotics from in situ rat small intestinal loops was studied at pH 7.4. For monobasic penicillins, despite the wide variety of apparent partition coefficients in isobutyl alcohol-water, the disappearance from the jejunal loops was almost 30% (+/- 5% SD). On the other hand, the disappearance of amphoteric derivatives of penicillins and cephalosporins having very low lipid solubility varied widely between 12 and 80%. The peak blood levels after intraduodenal administration to the rats correlated well with the extent of disappearance of amphoteric penicillins from the intestinal loops. Absorption studies utilizing in situ intestinal loops were performed at variable dose ranges to yield a clear dose-dependent disappearance. It is suggested that certain carrier-mediated transport systems underlie the absorption mechanism of amphoteric beta-lactam antibiotics.