1994 Volume 42 Issue Supplement4 Pages 243-250
The disposition of biapenem (BIPM), a new parenteral carbapenem antibiotic, was studied in mice, rats, dogs and monkeys. The plasma half-lives in dogs and monkeys were longer than those in mice and rats; the plasma half-lives of BIPM intravenously administered at a dose of 10mg/kg were 8.5 min in mice, 12.8 min in rats, 36.2 min in dogs and 37.0 min in monkeys. At a dose of 100mg/kg, the plasma half-lives of the animals were almost the same values as those at a 10mg/kg. The AUCs were dose-proportional to doses of 10 and 100mg/kg. These results suggest that the pharmacokinetics of BIPM undergoes on the linearity. Sex-difference was not observed in rat plasma levels of BIPM. The serum protein binding ratios in vitro were found to be as low as 3.7-10.2% in humans and lower than 6% in mice, rats, rabbits and dogs by the centrifugal ultra-filtration method at BIPM concentrations of 1, 10 and 100μg/rnl. In the presence of 10-5-10-4M of BIPM in vitro, bilirubin was not splitted out of its binding site on human serum albumin, being measured by the method of enzymatic oxidation of free bilirubin. It seems unlikely to augment free bilirubin in the presence of BIPM in vivo. BIPM was more stable than imipenem against partially purified renal dehydropeptidase-I obtained from mice, rats, swines, monkeys and humans. The urinary excretions of BIPM intravenously administered at a dose of 10mg/kg were 71.9% of dose in mice, 76.0% in rats, 64.7% in dogs and 63.2% in monkeys within 24 or 48 hours after dosing. The most portion of excreted amount was detected within the first 8 hours. At a 100mg/kg of dose, the percentage of urinary excretion attained to levels almost equal to those at a 10mg/kg.
