Percutaneous absorption and disposition studies of methotrexate in rabbits and rats.

The absorption and disposition of methotrexate (MTX) in the plasma, synovial fluid (SF), skin. and muscle tissue were studied following administration of a topical MTX gel in rabbits and rats. In rabbits, MTX concentrations in the plasma increased steadily toward the peak (5.9 ± 2.8 ng mL -1 ) which appeared at ∼2 h postdose and declined with the elimination half-life of 4.48 ± 1.74 h. At 1 h after the topical dose, the MTX concentrations in the skin (49.0 ± 19.8 μg g -1 ), muscle (12.7 ± 3.3 ng g -1 ), and SF (19.2 ± 10.1 ng g -1 ) underneath the dosed stifle joint were significantly higher (p 0.999) over the range of 2-50 ng mL -1 , quantitation limit of 0.5 ng mL -1 , and mean recovery of ∼87% was used for the quantitation of MTX in the tissue and fluid samples.