HEMODIALYSIS AND ENZYMATIC CLEAVAGE OF METHOTREXATE IN MAN

Renal insufficiency prolongs the serum half-life of methotrexate (MTX) and results in toxicity unless MTX can be removed, detoxified or its biochemical effects reversed. We studied the ability of hemodialysis and in vivo enzymatic cleavage with carboxypeptidase G1 (CPDG1) to reduce the serum MTX concentration in a patient with leukemia and renal failure. On three trials, a 5 hr hemodialysis failed to increase the serum MTX clearance or remove significant amounts of drug. On two trials, intravenous injection of CPDG1 caused an immediate 1.0-1.3 log unit fall in the MTX concentration measured by a kinetic enzyme assay, but only a minor change in MTX measured by radioimmunoassay. This difference is accounted for by crossreaction of the product of the enzymatic cleavage of MTX with the antibody used in the radioimmunoassay. This study demonstrates the inability to remove MTX from serum by hemodialysis in patients with high serum levels of MTX and poor renal function and defines some of the difficulties associated with enzymatic detoxification. © 1978.