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 of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic 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 affected by pretreatment with antacids.
Totsuka
K
K
Department of Medicine, Tokyo Women's Medical College, 8-1, Kawadacho, Shinjuku-ku, 162-8666, Tokyo, Japan.
Shimizu
K
K
Mori
N
N
Sugihara
T
T
Sakai
A
A
Yamaji
S
S
Michisuji
Y
Y
Shinohara
Y
Y
Kubo
A
A
Tokuoka
H
H
D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000328:Adult; D000863:Antacids / Q000008:administration & dosage* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015281:Cefmenoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011899:Ranitidine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014556:Urine / Q000737:chemistry
D000863:Antacids; D000900:Anti-Bacterial Agents; D011355:Prodrugs; C046817:cefteram pivoxil; C121334:ceftizoxime alapivoxil; D011899:Ranitidine; D015296:Ceftizoxime; D015281:Cefmenoxime