Excretion and metabolism of DA-7867, a new oxazolidinone, in rats.
Almost negligible hepatic metabolism (minor role of liver for the metabolism) and extensive urinary and fecal excretion of DA-7867 were investigated after intravenous administration at a dose of 10 mg/kg to rats. Pharmacokinetic parameters, especially nonrenal clearances of DA-7867, were very similar between control rats and rats pretreated with SKF 525-A, a nonspecific inhibitor of CYP isozymes, in rats. Similar results were also obtained between control rats and rats with liver cirrhosis induced by dimethylnitrosamine. Hepatic first-pass effect of DA-7867 was almost negligible in rats; the areas under the plasma concentration-time curve from time zero to time infinity of DA-7867 were not significantly different between intravenous and intraportal administration. The above data indicated that liver had almost negligible metabolic activity for DA-7867 in rats. Since metabolism of DA-7867 was not considerable in rats, urinary and fecal excretion of the drug was measured for up to 14 days in ten rats. Fecal excretion was the major route for elimination of DA-7867 in rats; approximately 85.0% of intravenous dose of DA-7867 at 10 mg/kg was recovered from urine (17.0% of intravenous dose), feces (64.0% of intravenous dose), washings of the metabolic cage (3.16% of intravenous dose), and entire gastrointestinal tract (0.421% of intravenous dose).
Bae
Soo K
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Shinlim-Dong, Kwanak-Gu, Seoul, Republic of Korea.
Kim
Eun J
EJ
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Inchul
I
Lee
Myung G
MG
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004128:Dimethylnitrosamine / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005243:Feces / Q000737:chemistry*; D007275:Injections, Intravenous; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply; D013997:Time Factors; D014018:Tissue Distribution
D000890:Anti-Infective Agents; C480487:DA-7867; D004791:Enzyme Inhibitors; D023303:Oxazolidinones; D011335:Proadifen; D004128:Dimethylnitrosamine