title: Distribution of methotrexate between plasma and peripheral lymph in man.
abstract: The distribution of methotrexate (MTX) to interstitial fluid has been studied by determination of MTX in peripheral lymph from the leg and in plasma after parenteral administration to 6 patients. Peak concentrations of MTX in lymph appear 0.5 to 3.25 h after peak concentrations in plasma. Maximal concentrations in lymph are 16 to 48% lower than in plasma. MTX concentration ratios lymph/plasma were higher than 1.0 (1.0-2.8) in 4 patients, and lower than 1.0 (0.2-0.8) in 2 patients. 12 to 34% of MTX was protein bound in lymph, but the variation in the ratio of bound to free MTX per g lymph protein was only 0.13 to 0.18. The patients with a lymph/plasma MTX ratio above 1.0 will have high and favourable MTX concentrations for distribution to tumours in peripheral tissue, while in the patients with a low ratio conditions for distribution are less favourable. The results indicate that pharmacokinetics of MTX are in accordance with a two or multicompartment model with varying distribution characteristics. The present observations indicate that distribution of MTX is blood flow limited, but the influence of permeability cannot be excluded.
mesh_terms: D000328:Adult; D006801:Humans; D007700:Kinetics; D007866:Leg; D008196:Lymph / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D008727:Methotrexate