title: Effective clearance of methotrexate using high-flux hemodialysis membranes.
abstract: We report the first series demonstrating effective clearance of methotrexate using acute intermittent hemodialysis with a high-flux dialyzer. The study was performed on six patients, two females and four males aged 13 to 72 years. All were patients at M.D. Anderson Cancer Center. Patients were dialyzed for 4 to 6 hours daily using a Fresenius F-80 membrane (Fresenius Inc, Walnut Creek, CA). Following the initiation of dialysis, there was a reduction in arterial and venous serum concentration of methotrexate with time. Mean plasma clearance of methotrexate during dialysis in these six patients was 92.1 +/- 10.3 mL/min. One patient who was nearly functionally anephric was studied in detail. In this patient, following a high dose of methotrexate (7.2 g/m2), approximately 63% of this dose was cleared with 6 hours of hemodialysis. With subsequent dialysis performed daily for 6 hours, the drug was cleared completely in 5.6 +/- 0.3 days (n = 7 separate methotrexate treatments). A reduction in plasma methotrexate concentration from 1,733 +/- 40 micromol/L 1 hour postinfusion to less than 0.3 micromol/L in 5 to 6 days was observed for these seven separate treatments. We conclude that significant clearance of methotrexate can be achieved with high-flux dialyzers, making methotrexate therapy a viable treatment option in patients with responsive malignancies despite the presence of renal failure.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Texas Medical School, Houston 77030, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Wall
authors.forename: M J
authors.initials: MJ
authors.lastname: Johansen
authors.forename: D A
authors.initials: DA
authors.lastname: Molony
authors.forename: T D
authors.initials: TD
authors.lastname: DuBose
authors.forename: N
authors.initials: N
authors.lastname: Jaffe
authors.forename: T
authors.initials: T
authors.lastname: Madden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D008727:Methotrexate / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D051437:Renal Insufficiency / Q000139:chemically induced / Q000150:complications / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D008567:Membranes, Artificial; D008727:Methotrexate