Effect of ionization on absorption of cephalosporins

To explore the relative absorbabilities of different ionic forms of cephalosporins, the absorption rates of four compounds were measured in the pH 5-9 region using an in situ rat gut technique. Cephalexin, cephradine, and cephaloglycin have some oral activity, while 3-[(acetyloxy)methyl]-8-oxo-7-[[(4-oxo-1(4H-pyridinyl)acetyl]-amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (I) has insignificant oral activity. The pH-species profiles calculated from their ionization constants showed that cephalexin, cephradine, and cephaloglycin have a large proportion of uncharged molecules plus zwitterions in the pH range of the small intestine, while I exists as the anion throughout this range. When the species profiles are compared with the pH-absorption rate profiles for cephalexin, cephradine, and I, the results are consistent with a model in which the zwitterionic and/or uncharged forms of the molecules are well absorbed, whereas the anions show little or no absorption. Although it has a pH profile for zwitterions plus uncharged molecules similar to cephalexin, cephaloglycin shows poor absorption, suggesting that the ratio of uncharged molecules to zwitterions may be important in absorption.