Effects of water deprivation for 72 hours on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats.

Abstract

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).

• Authors: Soo K Bae, Yu C Kim, Jae K Lee, Jong W Kwon, Moohi Yoo, Inchul Lee, Myung G Lee
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 27 Issue 3 Pg. 147-56 (Apr 2006) ISSN: 0142-2782 [Print] England
• PMID: 16408258 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2006 John Wiley & Sons, Ltd.

Chemical References

• Blood Proteins
• DA-7867
• Oxazolidinones

Topics

• Administration, Oral
• Animals
• Area Under Curve
• Blood Proteins (metabolism)
• Blood Urea Nitrogen
• Dehydration (physiopathology)
• Disease Models, Animal
• Eating (drug effects)
• Injections, Intravenous
• Liver (drug effects, pathology)
• Male
• Metabolic Clearance Rate
• Organ Size (drug effects)
• Oxazolidinones (administration & dosage, blood, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tissue Distribution
• Urination (drug effects)
• Water Deprivation (physiology)
• Weight Loss (drug effects)