Pharmacokinetic profile of methotrexate and 5-fluorouracil in normal and bilharzial-infested mice.
The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU), were investigated in normal and bilharzial-infested mice. Liver glucose-6-phosphatase activity and antipyrine clearance were used as parameters of liver function. Liver glucose-6-phosphatase activity was significantly reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a significant reduction in the elimination (beta) and clearance rate (Cl) of antipyrine, whereas its elimination half-life (t1/2 beta) was increased in comparison with the normal controls. A similar pattern was also obtained after MTX and 5-FU administration in bilharzial mice, compared to controls. These results indicate that hepatic bilharziasis causes a significant reduction in the hepatic clearance and elimination of MTX and 5-FU, whereas their areas under the concentration-time curve were significantly increased. These findings may have to be considered in the treatment of bilharzial cancer patients.
Osman
A M
AM
Cancer Biology Department, National Cancer Institute, Cairo, Egypt.
Saad
S F
SF
Saad
S Y
SY
el-Aaser
A B
AB
el-Merzabani
M M
MM
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006207:Half-Life; D008099:Liver / Q000201:enzymology; D008109:Liver Diseases, Parasitic / Q000201:enzymology / Q000378:metabolism; D008727:Methotrexate / Q000493:pharmacokinetics*; D051379:Mice; D012552:Schistosomiasis / Q000378:metabolism*
D005952:Glucose-6-Phosphatase; D000983:Antipyrine; D005472:Fluorouracil; D008727:Methotrexate