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.
|
Authors | Soo K Bae, Si H Yang, Shin J Lee, Jong W Kwon, Won B Kim, Duk C Lee, Myung G Lee |
Journal | European 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 |
PMID | 15911231
(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
|