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Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits.

Abstract：

: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.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Iven H,Brasch H,Engster J

doi

10.1007/BF00257520

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

115-20

issue

2

eissn

0344-5704

issn

1432-0843

journal_volume

15

pub_type

杂志文章

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