title: Pharmacokinetics, blood partition and protein binding of DA-7867, a new oxazolidinone.
abstract: 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 0.915 ml/min/kg. After consecutive 2 week oral administration at a dose of 2 mg/kg/day to rats, DA-7867 was accumulated in rats; the AUC was significantly greater (1430 versus 1880 micro g min/ml) than that after single oral administration at a dose of 2 mg/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 20 mg/kg. The rat tissues studied had almost negligible metabolic activity for DA-7867 based on 30 min incubation of DA-7867 with 9000 g supernatant fraction of rat tissues. DA-7867 was stable for up to 24 h 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 20 micro g/ml. The equilibrium of DA-7867 between plasma and blood cells of rabbit blood reached fast (within 30 s manual mixing), and the plasma-to-blood cell concentration ratios were independent of initial blood concentrations of DA-7867, 1-20 micro g/ml; the values ranged from 1.39 to 1.63. Protein binding of DA-7867 in five fresh rats plasma was 72.3%.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul, 151-742, Republic of Korea.
authors.forename: Soo K
authors.initials: SK
authors.lastname: Bae
authors.forename: Won-S
authors.initials: WS
authors.lastname: Chung
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kim
authors.forename: Jae K
authors.initials: JK
authors.lastname: Rhee
authors.forename: Jong W
authors.initials: JW
authors.lastname: Kwon
authors.forename: Won B
authors.initials: WB
authors.lastname: Kim
authors.forename: Myung G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D023303:Oxazolidinones / Q000097:blood* / Q000493:pharmacokinetics* / Q000652:urine; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; C480487:DA-7867; D023303:Oxazolidinones; D012709:Serum Albumin