Pharmacokinetics, blood partition and protein binding of DA-7867, a new oxazolidinone

The pharmacokinetics after single intravenous and single and consecutive 2 week oral administration, tissue distribution, in vitro tissue metabolism, stability, blood partition and protein binding of DA‐7867, a new oxazolidinone, were evaluated. After intravenous administration at a dose of 10mg/kg to rats, DA‐7867 was eliminated slowly with time‐averaged total body clearance of 0.915ml/min/kg. After consecutive 2 week oral administration at a dose of 2mg/kg/day to rats, DA‐7867 was accumulated in rats; the AUC was significantly greater (1430 versus 1880µg min/ml) than that after single oral administration at a dose of 2mg/kg. The rat tissues studied had low affinity to DA‐7867; the tissue‐to‐plasma ratios were smaller than unity after both intravenous and oral administration at a dose of 20mg/kg. The rat tissues studied had almost negligible metabolic activity for DA‐7867 based on 30min incubation of DA‐7867 with 9000 g supernatant fraction of rat tissues. DA‐7867 was stable for up to 24h incubation in various buffer solutions having pHs from 1 to 11, Sørensen phosphate buffer of pH 7.4, and rat plasma, urine and liver homogenate and 3h incubation in five human gastric juices. The binding of DA‐7867 to 4% human serum albumin was 50.6% at DA‐7867 concentrations ranging from 0.5 to 20µg/ml. The equilibrium of DA‐7867 between plasma and blood cells of rabbit blood reached fast (within 30s manual mixing), and the plasma‐to‐blood cell concentration ratios were independent of initial blood concentrations of DA‐7867, 1–20µg/ml; the values ranged from 1.39 to 1.63. Protein binding of DA‐7867 in five fresh rats plasma was 72.3%. Copyright © 2004 John Wiley & Sons, Ltd.