Pharmacokinetic Profile of Methotrexate and 5-Fluorouracil in Normal and Bilharzial-infested Mice

Abstract

The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU), were investigated in normal and bilharzial-infested mice. Liver glu-cose-6-phosphatase activity and antipyrine clearance were used as parameters of liver function. Liver glucose-6-phospha-tase activity was significantly reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a significant reduction in the elimination (β) and clearance rate (CI) of antipyrine, whereas its elimination half-life (t_½β) 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.

Pharmacokinetic–Pharmacodynamic Modeling of Methotrexate-Induced Toxicity in Mice

“…Our estimated values for clearance and half‐life are similar to those reported in female Swiss albino mice (clearance: 1.85 ± 0.07 L/kg/h; half life: 28.4 ± 2.4 min) after an i.p. bolus of 50 mg/kg 27. In our study, the mean peritoneal MTX concentration to plasma MTX concentration ratio ( R ) was 75, which is similar to the value reported for humans ( R = 92, peak peritoneal concentration/peak plasma concentration) 16…”

Efficiency of antioxidant Avenanthramide-C on high-dose methotrexate-induced ototoxicity in mice

“…The level of MTX in the bloodstream rapidly peaked 30 minutes after its administration in experimental mice, but decreased shortly thereafter, and was undetectable 8 hours later ( Fig 1B ) owing to uptake of MTX in the plasma, spleen, liver, gastrointestinal tract, kidney, muscles, skin, and bone marrow [ 18 ]. The plasma levels of MTX have been evaluated as a function of time in Abcc3 knockout (KO) and WT mice [ 19 ]. These mice were all administered a single dose of MTX (10, 50, and 200 mg/kg) through intravenous (IV) bolus.…”