Pharmacokinetics of 5-fluorouracil in rats with diabetes mellitus induced by streptozotocin

✍ Scribed by Young H. Choi; Ae K. Lee; Soo K. Bae; Sun O. Kim; Myung G. Lee

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 89 KB
• Volume: 26
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.436

✦ Synopsis

Abstract

The pharmacokinetic parameters of 5‐fluorouracil were compared after intravenous administration at a dose of 30 mg/kg to control Sprague–Dawley rats and to rats with diabetes mellitus induced by streptozotocin (DMIS). In DMIS rats, the area under the plasma concentration–time curve from time zero to time infinity (AUC) was significantly smaller (603 versus 909 µg min/ml) due to the significantly faster total body clearance (Cl; 47.8 versus 33.0 ml/min/kg). The faster Cl was due to the significantly faster renal (8.54 versus 4.02 ml/min/kg) and nonrenal (38.5 versus 28.7 ml/min/kg) clearances. In DMIS rats, the total amount of unchanged 5‐fluorouracil excreted in 24 h urine was significantly greater (34.1% versus 13.0% of intravenous dose) due to the urine flow rate‐dependent renal clearance of 5‐fluorouracil in rats (the greater the urine flow rate, the greater the urinary excretion of 5‐fluorouracil). Greater urinary excretion and a significantly smaller AUC resulted in a significantly faster Cl~r~ in DMIS rats. The faster Cl~nr~ in DMIS rats could be due to an increase in the expression and mRNA level of CYP1A1/2 in the rats. Copyright © 2005 John Wiley & Sons, Ltd.