Effects of protein-calorie malnutrition on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats.

Abstract

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.

• Authors: Soo Kyung Bae, Shin Jung Lee, Jong Won Kwon, Won Bae Kim, Myung Gull Lee
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 56 Issue 5 Pg. 635-42 (May 2004) ISSN: 0022-3573 [Print] England
• PMID: 15142341 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• DA-7867
• Dietary Proteins
• Oxazolidinones

Topics

• Administration, Oral
• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, urine)
• Area Under Curve
• Chromatography, High Pressure Liquid
• Dietary Proteins (pharmacology)
• Eating (drug effects)
• Feces (chemistry)
• Injections, Intravenous
• Male
• Malnutrition (metabolism)
• Oxazolidinones (administration & dosage, pharmacokinetics, urine)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tissue Distribution