Abstract
We studied the pharmacokinetics of S-1108, a new esterified oral cephem, in experimental animals. The oral absorption of S-1108 varied from species to species, and bioavailability in terms of ratio of oral/intravenous AUC was 33.7% in mice, 13.6% in rats, 5.7% in dogs and 21.0% in monkeys.
The peak plasma levels (Cmax) of S-1108 after oral administration of 20 mg/kg were 4.7 in mice, 1.8 in rats, 2.3 in rabbits, 1.2 in dogs and 3.6 μg/ml in monkeys, and the corresponding AUCs were 3.4, 5.8, 4.5, 4.4, and 10.6 μg·h/ml, respectively. In mice, rats and rabbits, the plasma levels of S-1108 were lower in comparison with cefteram pivoxil (CFTM-PI), but they were higher than with CFTM-PI in monkeys, and equal to those of CFTM-PI in dogs.
The tissue levels of S-1108 in rats after oral administration were highest the kidney, followed in descending order by the plasma, liver, lung, heart and spleen.
Urinary excretion rates of S-1108 were 7.1% in mice, 22.7% in rats, 23.9% in rabbits, 15.9% in dogs and 16.0% in monkeys.
Biliary excretion rates of S-1108 after oral administration were 2.0% in rats.
Plasma levels of S-1108 after oral administration in the non-fasting state were increased in rats and dogs, but decreased in monkeys.
No antimicrobially active metabolites except S-1006, the bioactive farm of S-1108, were detected in the plasma or urine samples.
The binding of S-1006 to serum protein was 27% in mice, 28% in rats, 62% in monkeys and 46% in humans, and their values were all lower than in the case of CFTM.
