Intestinal absorption mechanism of amphoteric beta-lactam antibiotics II: Michaelis-Menten kinetics of cyclacillin absorption and its pharmacokinetic analysis in rats

Tsuji, A.; Nakashima, E.; Kagami, I.; Yamana, T.

Journal of Pharmaceutical Sciences 70(7): 772-777

1981


ISSN/ISBN: 0022-3549
PMID: 7264925
DOI: 10.1002/jps.2600700715
Accession: 005735336

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Abstract
The absorption of cyclacillin at pH 7.0 by the rat small intestine was investigated using in situ perfusion. At the lowest dose of 95 .mu.g/ml, the antibiotic disappearance was rapid and followed 1st-order kinetics, with the disappearance being 85% at 100 min. At the intermediate concentrations of 770 and 1200 .mu.g/ml, the disappearance after 100 min was 69 and 54%, respectively, and semilogarithmic plots clearly showed convex curvatures. At the highest concentration of 30 mg/ml, cyclacillin disappeared slowly from the perfusate, in an apparent 1st-order fashion. The disappearence was 26% after 100 min of perfusion and was similar in extent at 5.2 mg/ml. This concentration-time profile was satisfactorily fitted to the simultaneous Michaelis-Menten and 1st-order kinetic equations. The area under the blood concentration vs. time curve (AUC) after a single intraduodenal dose of cyclacillin was almost consistent with the AUC after the equivalent i.v. dose (10 mg/kg). Additional evidence from a pharmacokinetic analysis of steady-state blood concentrations after constant infusion of cyclacillin through the portal vein and the small intestinal lumen indicated that cyclacillin absorption by the rat intestinal tissue at relatively low concentrations (< 1 mg/ml) followed solely Michaelis-Menten kinetics. Cyclacillin may be transported by certain types of carrier-mediated mechanisms.

Intestinal absorption mechanism of amphoteric beta-lactam antibiotics II: Michaelis-Menten kinetics of cyclacillin absorption and its pharmacokinetic analysis in rats