PHARMACOKINETICS AND SAFETY OF BO-2727, A NEW INJECTABLE 1-BETA-METHYL CARBAPENEM ANTIBIOTIC, AND ITS EFFECT ON THE FECAL MICROFLORA IN HEALTHY MALE-VOLUNTEERS

The safety and pharmacokinetics of BO-2727, a new injectable 1-β-methyl carbapenem antibiotic, and its effect on the faecal microflora were evaluated in single- and multiple-dose studies involving twenty-four healthy male adult volunteers following a preliminary safety evaluation of 25, 50 and 125 mg iv doses in six volunteers. BO-2727 was administered by iv infusion over 30 min. There was a good correlation between BO-2727 concentrations assayed by HPLC and a microbiological method; the HPLC results were used in the pharmacokinetic analysis. The single-dose study indicated that plasma concentration versus time curves at doses of 250, 500 and 1000 mg were well described by a two-compartment open model. The mean (±S.D.) elimination half-life ranged from 1·41±0·21 h to 1·54±0·10 h, and the peak plasma concentrations (Cmax) and the area under the plasma concentration versus time curves increased linearly with the dose. The mean urinary recoveries within the first 24 h were 70·63±5·24% to 77·38±4·55% of the dose. The highest concentration of BO-2727 in saliva was 0·72 mg/L which was reached 1 h after the start of the 1000 mg infusion and accounted for approximately 1% of the Cnax. No BO-2727 was found in faecal samples collected 24 and 48 h after a single 1000 mg dose. In the multiple-dose study, BO-2727 500 mg bd was administered for 4·5 days. There were no obvious differences in plasma concentrations and urinary recoveries between the single- and multiple-dose regimens. BO-2727 did not accumulate as determined by plasma concentrations and urinary recoveries. No marked changes in the aerobic and anaerobic faecal microflora were observed during multiple-dose administration. There were no significant adverse reactions, and likewise no abnormalities in physical and laboratory examinations that were definitely related to the drug. © 1994 The British Society for Antimicrobial Chemotherapy.