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.
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.