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 (10 mg/kg) to control Sprague–Dawley rats and DMIS rats (at 7th and 29th days after administration of streptozotocin, 45 mg/kg). After i.v. administration to DMIS rats, the AUC0–∞ 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 (Ae0–24 h). The greater Ae0–24 h in DMIS rats could be due to urine flow rate-dependent renal clearance of DA-7867. After oral administration to DMIS rats, the AUC0–∞ 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 Ae0–24 h 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.