Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits.
In rabbits the IV kinetics of MTX (1.33, 4 and 12 mg/kg) could be described by a linear three-compartment model with a terminal half-life between 2.4 and 3.6 h. During 8 h 50% of the dose was excreted into urine in unchanged form and 15% as the metabolite 7-OH-MTX. These fractions remained constant with increasing dose. In continuous infusion experiments (9-900 micrograms/kg X min MTX IV) a decrease of the renal MTX clearance with increasing plasma concentration was observed. This effect was nearly compensated by an increase of the extrarenal MTX clearance. After short-term infusion of 7-OH-MTX (4 mg/kg) a biexponential decline of 7-OH-MTX plasma concentrations was observed with a terminal half-life of 0.45 h. About 80% of the dose was regained from urine during 5 h. From the combined pharmacokinetic data a linear model was constructed for the calculation of 7-OH-MTX plasma concentrations after short-term MTX infusion. For the first 4 h after MTX application the predicted values were in good accordance with the 7-OH-MTX concentrations actually measured.
D000818:Animals; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D008954:Models, Biological; D011817:Rabbits
C011864:7-hydroxymethotrexate; D008727:Methotrexate