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.
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.
Bae
Soo K
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Yang
Si H
SH
Lee
Shin J
SJ
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Duk C
DC
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
C480487:DA-7867; D023303:Oxazolidinones; D013311:Streptozocin