Pharmacokinetics and safety of BO-2727, a new injectable 1-beta-methyl carbapenem antibiotic, and its effect on the faecal microflora in healthy male volunteers.
The safety and pharmacokinetics of BO-2727, a new injectable 1-beta-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 Cmax. 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.
Nakashima
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Uematsu
T
T
Kosuge
K
K
Nakagawa
S
S
Hata
S
S
Sanada
M
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001774:Blood Chemical Analysis; D015780:Carbapenems / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004285:Dogs; D005243:Feces / Q000382:microbiology*; D006207:Half-Life; D000882:Haplorhini; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D010865:Pilot Projects; D051381:Rats
D000890:Anti-Infective Agents; D015780:Carbapenems; C085890:BO 2727