Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic - comparison with cefteram-pivoxil

The effect of pretreatment with ranitidine, an antacid, on the absorption o f AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime ( CTIZ), was examined in eight healthy adult male volunteers by the cross-ove r method, using cefteram-pivoxil (CTER-PI) as the control drug. The C-max a nd area under the concentration (AUC) values and cumulative urinary excreti on rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreas ed by 32, 38 and 37%, respectively, in the ranitidine pretreatment group wh ereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibi otics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affe cted by pretreatment with ranitidine largely due to inactivation of this an tibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be a ffected by pretreatment with antacids. (C) 2001 Published by Elsevier Scien ce B.V. and International Society of Chemotherapy.