Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes

Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 M) in three selected intestinal segments and one cefuroxime axetil solution (118 muM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k(ap) and effective permeability coefficients, P-eff, were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis-Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: V-m = 0.613 (0.440) muM min(-1); K-m = 31.49(28.31) muM and k(a) = 0.011(0.003) min(-1). Parameters characterizing degradation of the prodrug were obtained in each intestinal segment: proximal segment k(dp) = 0.0049(0.0003) min(-1), mean segment, k(dm) = 0.0131(0.0007) min(-1) and distal segment k(dd)=0.019(0.0009) min(-1). Therefore, in situ intestinal absorption of cefuroxime axetil in the proximal segment of the rat in the presence of variable concentrations of cefadroxil has been investigated in order to examine the inhibitory effect of cefadroxil on cefuroxime axetil transport. The data suggest that cefadroxil and cefuroxime axetil share the same intestinal carrier. (C) 2002 Elsevier Science B.V. All rights reserved.