Abstract
Phase I studies of S-1108, a new ester-type oral cephem antibiotic, were conducted on 61 healthy male volunteers. In single-dose studies, S-1108 was administered under fasting and non-fasting conditions in various amounts. In multiple-dose studies, 150 mg of S-1108 was administered three times daily for 8 days. Plasma concentrations and urinary recoveries of the active form S-1006 were determined in these studies. The results for tolerance, safety and pharmacokinetic profile of S-1108 in these studies are summarized below.
1. S-1108 was well tolerated and this drug was found to be safe in these studies.
2. Elimination half-lives and urinary recoveries of S-1006 were shown to be almostconstant regardless of dose administered in the single-dose studies. The Cmax and AUC of S-1006 were proportional to the dose, suggesting linearity of the pharmacokinetics of S-1108.
3. AUC and urinary recovery increased significantly when S-1108 was given after a meal, suggesting that absorption of S-1006 under non-fasting conditions is greater than under fasting conditions.
4. No abnormal accumulation or changes in the pharmacokinetic parameters of S-1108 were found in the multiple-dose study.
5. After administration of S-1108, S-1006 and trace amounts of trans-S-1006 were found in the blood and urine. No unchanged S-1108 or other active metabolites were found.
