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Pharmacokinetic changes of DA-7867, a new oxazolidinone, after intravenous and oral administration to rats with short-term and long-term diabetes mellitus induced by streptozotocin.

Abstract
Effects of diabetes mellitus induced by streptozotocin (DMIS) on the pharmacokinetics of DA-7867 were investigated after i.v. and oral administration (10mg/kg) to control Sprague-Dawley rats and DMIS rats (at 7th and 29th days after administration of streptozotocin, 45mg/kg). After i.v. administration to DMIS rats, the AUC(0-infinity) values were significantly smaller (50.7 and 64.8% decrease for 7th and 29th days, respectively); this could be due to significantly faster Cl values in the rats (127 and 183% increase for 7th and 29th days, respectively). The faster Cl values were mainly due to significantly greater amount of unchanged drug excreted in 24-h urine (Ae(0-24h)). The greater Ae(0-24h) in DMIS rats could be due to urine flow rate-dependent renal clearance of DA-7867. After oral administration to DMIS rats, the AUC(0-infinity) values were also significantly smaller (61.3 and 72.6% decrease for 7th and 29th days, respectively); this could also be mainly due to significantly greater Ae(0-24h) in the rats. Streptozotocin-induced hepatotoxicity did not influence considerably on the pharmacokinetics of DA-7867 at 7th day when compared with those at 29th day.
AuthorsSoo K Bae, Si H Yang, Shin J Lee, Jong W Kwon, Won B Kim, Duk C Lee, Myung G Lee
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 25 Issue 2-3 Pg. 337-45 (Jun 2005) ISSN: 0928-0987 [Print] Netherlands
PMID15911231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DA-7867
  • Oxazolidinones
  • Streptozocin
Topics
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Diabetes Mellitus, Experimental (metabolism)
  • Injections, Intravenous
  • Male
  • Metabolic Clearance Rate
  • Oxazolidinones (administration & dosage, pharmacokinetics)
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Time Factors

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