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 10mg kg−1 to control rats and rats with protein-calorie malnutrition (rats with PCM). After intravenous administration of 10mg 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 6990μg min mL−1) compared with control rats. This may have been due to significantly faster total body clearance (CL, 0.930 vs 1.44mL min−1 kg−1). The faster CL in PCM rats could have been due to significantly faster non-renal clearance (0.842 vs 1.39mL min−1 kg−1 due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867 recovered from the entire gastrointestinal tract at 24h was significantly greater (1.19 vs 4.28% of intravenous dose)) because the renal clearance was significantly slower in PCM rats (0.0874 vs 0.0553mL min−1 kg−1). After oral administration to PCM rats, the AUC was significantly smaller compared with control rats (7900 vs 4310μgmin mL−1). This could have been due to a decrease in absorption from the gastrointestinal tract.