Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits

✍ Scribed by Heiko Iven; Helmut Brasch; Jörg Engster

• Publisher: Springer
• Year: 1985
• Tongue: English
• Weight: 551 KB
• Volume: 15
• Category: Article
• ISSN: 0344-5704
• DOI: 10.1007/bf00257520

✦ Synopsis

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.