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 multicom-

partment 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.