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

Article Details

Citation

Choi YH, Lee AK, Bae SK, Kim SO, Lee MG

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

Biopharm Drug Dispos. 2005 Apr;26(3):93-8.

PubMed ID
15674819 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
StreptozocinCytochrome P450 1A1ProteinHumans
Unknown
Inducer
Details
StreptozocinCytochrome P450 1A2ProteinHumans
Unknown
Inducer
Details