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

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

Research output: Contribution to journalArticle

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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 μl/ml, the antibiotic disappearance was rapid and followed first-order kinetics, with the disappearance being 85% at 100 min. At the intermediate concentrations of 770 and 1200 μg/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 first-order fashion. The disappearance 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 first-order kinetic equations. The area under the blood concentration versus time curve (AUC) after a single intraduodenal dose of cyclacillin was almost consistent with the AUC after the equivalent intravenous 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.

Original languageEnglish
Pages (from-to)772-777
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume70
Issue number7
Publication statusPublished - 1981
Externally publishedYes

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Cyclacillin
Lactams
Pharmacokinetics
Intestinal Absorption
Rats
Anti-Bacterial Agents
Kinetics
Area Under Curve
Blood
Perfusion
Portal Vein
Small Intestine
Tissue

ASJC Scopus subject areas

  • Molecular Medicine
  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Pharmacology

Cite this

Intestinal absorption mechanism of amphoteric β-lactam antibiotics. II. Michaelis-Menten kinetics of cyclacillin absorption and its pharmacokinetic analysis in rats. / Tsuji, A.; Nakashima, E.; Kagami, I.; Yamana, T.

In: Journal of Pharmaceutical Sciences, Vol. 70, No. 7, 1981, p. 772-777.

Research output: Contribution to journalArticle

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AU - Nakashima, E.

AU - Kagami, I.

AU - Yamana, T.

PY - 1981

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