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

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Abstract
The pharmacokinetics of 1-oxa-β-lactam (LY127935), a new semisynthetic β-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 μg/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 μg/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 μg/ml after completion of the i.v. infusion and 4.8 ± 0.7 μg/ml after the i.m. injection. The mean serum half-lives for the β 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 μg/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.

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