Interactions of methotrexate and cyclophosphamide with the pharmacokinetics of 5-fluorouracil in an animal model.
The interaction of methotrexate and/or cyclophosphamide with the pharmacokinetics of 5-fluorouracil (5-FU) was studied in tumor-bearing WAG/Rij rats. Four groups were formed including treatment with single-agent 5-FU (eight rats); 5-FU plus methotrexate (11 rats); 5-FU plus cyclophosphamide (12 rats); and 5-FU, cyclophosphamide, and methotrexate (13 rats). The area-under-the-plasma-concentration/time curve, total-body clearance, elimination half-life, mean residence time, and steady-state volume of distribution were computed and compared. The mean residence time and elimination half-life of 5-FU increased when methotrexate was included in the combination. The increase was significant (P less than 0.05) for 5-FU, cyclophosphamide, and methotrexate versus 5-FU and cyclophosphamide.
Department of Pharmacology, University of Leiden, The Netherlands.
E A
EA
de Bruijn
O
O
Driessen
P
P
Leeflang
E
E
van Strijen
N
N
van den Bosch
J
J
Hermans
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology*; D051381:Rats
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate