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  • Title: Folic acid alters methotrexate availability in patients with rheumatoid arthritis.
    Author: Bressolle F, Kinowski JM, Morel J, Pouly B, Sany J, Combe B.
    Journal: J Rheumatol; 2000 Sep; 27(9):2110-4. PubMed ID: 10990220.
    Abstract:
    OBJECTIVE: To evaluate the effects of repeated doses of folic acid on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: We studied 20 patients (ages 30-78 years) who received MTX intramuscularly (10 mm/week). MTX was administered alone or after treatment with folic acid (5 mg tablet once daily) for 13 days. Plasma samples were collected 2 and 8 h after dose intake. MTX concentrations in plasma and ultrafiltrate samples were measured by fluorescence polarization immunoassay. A Bayesian approach was used to determine individual MTX pharmacokinetic variables to minimize the number of samples collected. RESULTS: Folic acid supplementation led to reduced plasma MTX levels 2 and 8 h after MTX administration and reduced area under the plasma MTX concentration versus time curve (AUC) (about 20%; p < 0.02). Total clearance of MTX and Vd were higher when patients were also receiving folic acid than when they were taking MTX alone (p < 0.02). The plasma protein binding of MTX remains unchanged. CONCLUSION: The lower plasma MTX concentrations in patients taking folic acid supplements could be interpreted as increased cellular uptake of MTX; the folic acid supplements would promote the sequestering of MTX intracellularly. The decrease of MTX concentrations leads to reduced AUC; it is also possible that there are reduced AUC combined with increased intracellular folate levels. These results reopen the question of whether folic acid should be used immediately in all patients when MTX is begun.
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