Pharmacokinetics of DA-7218, a new oxazolidinone, and its active metabolite, DA-7157, after intravenous and oral administration of DA-7218 and DA-7157 to rats.
DA-7218 (a prodrug of DA-7157), a new oxazolidinone, was hydrolysed via phosphatase to form its active metabolite, DA-7157, in rats. The pharmacokinetic parameters of DA-7218 and DA-7157 were evaluated after intravenous (5, 10 and 20 mg kg(-1)) and oral (20, 50 and 100 mg kg(-1)) administration of DA-7218 to rats. DA-7218 and DA-7157 exhibited dose-proportional pharmacokinetics after both intravenous and oral administration of DA-7218 to rats. The stability of DA-7218 and DA-7157, blood partition of DA-7157, and the plasma protein binding of DA-7157 were also evaluated. DA-7218 was unstable in rat blood, plasma, bile and liver homogenates, but DA-7157 was stable, suggesting that DA-7218 is hydrolysed via phosphatase. DA-7157 rapidly reached equilibrium between plasma and blood cells, and the mean equilibrium plasma-to-blood cells ratio was 3.18, indicating that binding of DA-7157 to blood cells was not considerable. The protein binding of DA-7157 in fresh rat plasma was 93.4%.
Bae
Soo K
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Yang
Si H
SH
Shin
Karen N
KN
Rhee
Jae K
JK
Yoo
Moohi
M
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D010755:Organophosphates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010080:Oxazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; C515039:DA 7157; D010755:Organophosphates; D010080:Oxazoles; D023303:Oxazolidinones; D011355:Prodrugs; D013777:Tetrazoles; C515040:tedizolid phosphate