da-7867 and Weight-Loss

The pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg in control rats and in rats with water deprivation for 72 h (rat model of dehydration). After intravenous administration in the rat model of dehydration, the Cl(nr) (0.654 versus 0.992 ml/min/kg) and Cl(r) (0.0273 versus 0.0784 ml/min/kg) values were significantly slower than in the controls. The slower Cl(nr) could be due mainly to a significantly smaller total amount of unchanged DA-7867 recovered from the gastrointestinal tract at 24 h (GI(24 h): 5.16% versus 9.21% of intravenous dose) due to impaired liver function in the rat model of dehydration. The slower Cl(r) could be due mainly to a significantly smaller 24 h urinary excretion of unchanged drug (Ae(0-24 h): 4.41% versus 7.75% of intravenous dose) due to urine flow rate-dependent Cl(r) of DA-7867 in the rat model of dehydration. Hence, the Cl was significantly slower in the rat model of dehydration (0.677 versus 1.07 ml/min/kg). After intravenous administration in the rat model of dehydration, the V(ss) of DA-7867 was significantly smaller than in the controls (396 versus 506 ml/kg) due mainly to significantly smaller free (unbound to plasma proteins) fractions of DA-7867 in plasma (6.90% versus 29.2%) in the rat model of dehydration. After oral administration in the rat model of dehydration, the AUC was significantly greater than that in controls (10800 versus 7060 microg min/ml) due mainly to a significantly smaller Ae(0-24 h) than in controls (3.50% and 6.17% of oral dose).

Topics: Administration, Oral; Animals; Area Under Curve; Blood Proteins; Blood Urea Nitrogen; Dehydration; Disease Models, Animal; Eating; Injections, Intravenous; Liver; Male; Metabolic Clearance Rate; Organ Size; Oxazolidinones; Rats; Rats, Sprague-Dawley; Time Factors; Tissue Distribution; Urination; Water Deprivation; Weight Loss