Characterization of the oral absorption of beta-lactam antibiotics. I. Cephalosporins: determination of intrinsic membrane absorption parameters in the rat intestine in situ.

The oral absorption of five cephalosporin antibiotics, cefaclor, cefadroxil, cefatrizine, cephalexin, and cephradine, has been studied using a single-pass intestinal perfusion technique in rats. Intrinsic membrane absorption parameters, "unbiased" by the presence of an aqueous permeability (diffusion or stagnant layer), have been calculated utilizing a boundary layer mathematical model. The resultant intrinsic membrane absorption parameters are consistent with a significant carrier-mediated, Michaelis-Menten-type kinetic mechanism and a small passive component in the jejunum. Cefaclor colon permeability is low and does not exhibit concentration dependent behavior. The measured carrier parameters (+/- SD) for the jejunal perfusions are as follows: cefaclor, J*max = 21.3 (+/- 4.0), Km = 16.1 (+/- 3.6), P*m = 0, and P*c = 1.32 (+/- 0.07); cefadroxil, J*max = 8.4 (+/- 0.8), Km = 5.9 (+/- 0.8), P*m = 0, and P*c = 1.43 (+/- 0.10); cephalexin, J*max = 9.1 (+/- 1.2), Km = 7.2 (+/- 1.2), P*m = 0, and P*c = 1.30 (+/- 0.10); cefatrizine, J*max = 0.73 (+/- 0.19), Km = 0.58 (+/- 0.17), P*m = 0.17 (+/- 0.03), and P*c = 1.25 (+/- 0.10); and cephradine, J*max = 1.57 (+/- 0.84), Km = 1.48 (+/- 0.75), P*m = 0.25 (+/- 0.07), and P*c = 1.06 (+/- 0.08). The colon absorption parameter for cefaclor is P*m = 0.36 (+/- 0.06, where J*max (mM) is the maximal flux, Km (mM) is the Michaelis constant, P*m is the passive membrane permeability, and P*c is the carrier permeability.(ABSTRACT TRUNCATED AT 250 WORDS)