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

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 microg 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.

• Authors: Young H Choi, Ae K Lee, Soo K Bae, Sun O Kim, Myung G Lee
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 26 Issue 3 Pg. 93-8 (Apr 2005) ISSN: 0142-2782 [Print] England
• PMID: 15674819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 John Wiley & Sons, Ltd.

Chemical References

• Fluorouracil

Topics

• Animals
• Chromatography, High Pressure Liquid
• Diabetes Mellitus, Experimental (metabolism)
• Fluorouracil (administration & dosage, blood, pharmacokinetics, urine)
• Injections, Intravenous
• Male
• Metabolic Clearance Rate
• Rats
• Rats, Sprague-Dawley