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
Tsuji, A.; Nakashima, E.; Kagami, I.; Yamana, T.
Journal of Pharmaceutical Sciences 70(7): 768-772
ISSN/ISBN: 0022-3549 PMID: 7264924 DOI: 10.1002/jps.2600700714
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). 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 using in situ intestinal loops were performed at variable dose ranges to yield a clear dose-dependent disappearance. Certain carrier-mediated transport systems may underlie the absorption mechanisms of amphoteric .beta.-lactam antibiotics.