Effects of protein-calorie malnutrition on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats.
The pharmacokinetic parameters of DA-7867, a new oxazolidinone, were compared after intravenous and oral administration at a dose of 10 mg x kg(-1) to control rats and rats with protein-calorie malnutrition (rats with PCM). After intravenous administration of 10 mg x kg(-1) DA-7867 to rats, metabolism of the drug was not considerable and after 14 days approximately 85.0% of the dose was recovered as unchanged drug from urine and faeces. After intravenous administration to rats with PCM, the area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (10800 vs 6990 microg min x mL(-1)) compared with control rats. This may have been due to significantly faster total body clearance (CL, 0.930 vs 1.44 mL x min(-1) x kg(-1)). The faster CL in PCM rats could have been due to significantly faster non-renal clearance (0.842 vs 1.39 mL x min(-1) x kg(-1) due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867 recovered from the entire gastrointestinal tract at 24 h was significantly greater (1.19 vs 4.28% of intravenous dose)) because the renal clearance was significantly slower in PCM rats (0.0874 vs 0.0553 mL x min(-1) x kg(-1)). After oral administration to PCM rats, the AUC was significantly smaller compared with control rats (7900 vs 4310 microg x min x mL(-1)). This could have been due to a decrease in absorption from the gastrointestinal tract.
Bae
Soo Kyung
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
Lee
Shin Jung
SJ
Kwon
Jong Won
JW
Kim
Won Bae
WB
Lee
Myung Gull
MG
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004044:Dietary Proteins / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; C480487:DA-7867; D004044:Dietary Proteins; D023303:Oxazolidinones