Intestinal absorption mechanism of amphoteric β‐lactam antibiotics II: Michaelis—menten kinetics of cyclacillin absorption and its pharmacokinetic analysis in rats

Akira Tsuji, Emi Nakashima, Izumi Kagami, Tsukinaka Yamana

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 μ/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 μ/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
DOIs
Publication statusPublished - 1981 Jul

Keywords

  • Absorption kinetics—rat intestinal loops, blood cyclacillin levels after intravenous, intraportal, and intraduodenal administration
  • Antibiotics, amino‐β‐lactam—cyclacillin, in situ intestinal absorption kinetics, blood levels after intravenous, intraportal, and intraduodenal administration to rats
  • Cyclacillin—intestinal absorption kinetics in situ, blood levels in rats after intravenous, intraportal, and intraduodenal administration
  • Kinetics, absorption—blood cyclacillin levels after intravenous, intraportal, and intraduodenal administration, in situ rat intestinal loops
  • Pharmacokinetics—cyclacillin, intestinal absorption in situ, blood levels after intravenous, intraportal, and intraduodenal administration to rats

ASJC Scopus subject areas

  • Pharmaceutical Science

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