Pharmacology of a New 1-Oxa-β-lactam (LY127935) in Normal Volunteers

The pharmacokinetics of 1-oxa-beta-lactam (LY127935), a new semisynthetic beta-lactam antibiotic, was studied in four healthy adult volunteers (mean age of 27 years, mean body surface area +/- standard error SE of 1.87 +/- 0.08 m(2), and mean creatinine clearance +/- SE of 116 +/- 12 ml/min per 1.73 m(2)). Immediately after completion of a 1-g, 20-min intravenous (i.v.) infusion, the mean serum level +/- SE was 70.7 +/- 8.5 mug/ml. After a 1-g intramuscular (i.m.) injection, peak serum levels occurred from 30 min to 1 h, and the mean peak serum level +/- SE was 52.3 +/- 1.6 mug/ml. Beginning at 1 h, the serum concentrations after i.m. administration were higher than those after i.v. administration. At 8 h, the mean serum level +/- SE was 3.8 +/- 0.6 mug/ml after completion of the i.v. infusion and 4.8 +/- 0.7 mug/ml after the i.m. injection. The mean serum half-lives for the beta phase i.v. and i.m. administration were similar (2.3 +/- 0.7 h and 2.4 +/- 0.2 h, respectively). The mean apparent volume of distribution +/- SE was 16.6 +/- 1.9 liters per 1.73 m(2). The mean serum clearance +/- SE of LY127935 was 85.4 +/- 12.7 ml/min per 1.73 m(2), and the mean renal clearance +/- SE was 54.5 +/- 4.4 ml/min per 1.73 m.(2) Urine concentrations of LY127935 were at least 140 mug/ml in each volunteer during the first 12 h after i.m. or i.v. administration. The mean percentages of the dose recovered in the urine +/- SE within 2 h after i.v. or i.m. administration were similar (30 +/- 4 and 34 +/- 11, respectively). Only 67 +/- 3% and 75 +/- 13% were recovered in the urine within 24 h after i.v. and i.m. administration, respectively.