Leucovorin p.o. was as effective as parenterally in pre venting weight loss and toxic deaths in normal mice from high doses of methotrexate. Histological sections of proxi mal jejunum demonstrate the protection afforded by de layed p.o. leucovorin from the marked disruption of villi and mucosal glands produced by methotrexate. Mice bearing leukemia L1210 treated with methotrexate plus leucovori...

A 52-year-old woman presented herself with pain on the medial sides of the proximal tibia after a minimal trauma. Conventional X-rays did not show any pathology. However, the MRI showed a bilateral fracture of the proximal tibia. Since the patient was treated with methotrexate due to rheumatoid arthritis, methotrexate osteopathy was considered. Long term treatment with low doses of methotrexate...

Objective To evaluate the efficacy of etanercept and methotrexate as monotherapies and as combination therapy in subjects with active psoriatic arthritis (PsA). Methods The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) is an ongoing, global, double-blind, 48-week, randomised, controlled study. Subjects are randomised (1:1...

Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD) model was built with NONMEM. Several compartment and indirect response models were inv...

5-Formyltetrahydrofolate was found to reverse the binding of methotrexate to dihydrofolate redactase in the Ehrlich ascites tumor in vitro. When cells pretreated with methotrexate were resuspended in methotrexate-free buffer containing 5-formyltetrahydrofolate (or 5-methyltetrahydrofolate), net dissociation of the antifolate from the enzyme was observed. Methotrexate associated with the enzyme ...

The aim of this study was to investigate the functional importance of multidrug resistance-associated protein (Mrp)3/Abcc3 and Mrp4/Abcc4 in the pharmacokinetics of methotrexate. Compared with the corresponding wild-type mice, the plasma concentrations of methotrexate given orally were similar in Abcc4(-/-) mice and were significantly lower in Abcc3(-/-) mice. Pharmacokinetic parameters related...

OBJECTIVES To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphyloc...

Background: Alopecia areata is one of the most common human autoimmune disorders and its severe types are refractory to all conventional therapies. Corticosteroids have been used in severe alopecia areata since 1950s but there is concern over complications caused by high doses of corticosteroids. Methotrexate has been used as an adjunctive therapy in some autoimmune disorders and has been propo...

This study reports the isolation and characterization of a variant of the human CCRF-CEM leukemia cell line that overproduces the carrier protein responsible for the uptake of reduced folates and the folate analogue methotrexate. The variant was obtained by adapting CCRF-CEM cells for prolonged times to stepwise decreasing concentrations of 5-formyltetrahydrofolate as the sole folate source in ...

Thymidine rescue was administered following 63 courses of high-dose methotrexate in 20 patients. In the first part of this study, the methotrexate was given as a 24-hr infusion and the dose was escalated from 0.14 to 8.54 g/sq m; in the second part, methotrexate was infused to maintain a serum concentration of 15 micrometer for 30, 36, or 40 hr. Thymidine rescue was started immediately after th...