Folic acid alters methotrexate availability in patients with rheumatoid arthritis

Objective, To evaluate the effects of repeated doses of folic acid on the p harmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis . Methods. We studied 20 patients (ages 30-78 years) who received MTX intramu scularly (10 mm/week). MTX was administered alone or after treatment with f olic acid (5 mg tablet once daily) for 13 days. Plasma samples were collect ed 2 and 8 h after dose intake. MTX concentrations in plasma and ultrafiltr ate samples were measured by fluorescence polarization immunoassay. A Bayes ian 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 concentr ation 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 re mains unchanged. Conclusion. The lower plasma MTX concentrations in patients taking folic ac id supplements could be interpreted as increased cellular uptake of MTX: th e folic acid supplements would promote the sequestering of MTX intracellula rly. The decrease of MTX concentrations leads to reduced AUG; it is also po ssible that there are reduced AUC combined with increased intracellular fol ate levels, These results reopen the question of whether folic acid should be used immediately in all patients when MTX is begun.