title: Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion.
abstract: This article documents the case of a patient with severe renal failure immediately after having been given high-dose methotrexate; the patient was effectively treated with repeated hemodialysis, charcoal hemoperfusion, leucovorin, and thymidine. The methotrexate plasma concentration was reduced from 390 mumol/L to 7 mumol/L as a result of 24.5 hours of hemodialysis along with 39.5 hours of hemoperfusion. Although a rebound in the plasma methotrexate concentration occurred the first three times that hemodialysis and/or hemoperfusion was stopped, reinstitution of the procedure was always effective in further lowering methotrexate concentrations. The patient was subsequently managed with leucovorin and thymidine rescue. Simultaneous measurements before and after the hemodialysis-hemoperfusion apparatus and before and after the hemoperfusion device alone revealed a percent decrease in the concentration of d-leucovorin of 36% and 79%; 1-leucovorin, 82% and 75%; 5-methyltetrahydrofolate, 52% and 64%; methotrexate, 73% and 37%; and 7-hydroxymethotrexate, 21% and 24%, respectively. Gastrointestinal and hematologic toxicities were completely prevented, and serum creatinine normalized within 24 days.
authors.affiliation: Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
authors.forename: F B
authors.initials: FB
authors.lastname: Stapleton
authors.forename: J
authors.initials: J
authors.lastname: Ochs
authors.forename: D P
authors.initials: DP
authors.lastname: Jones
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: I W
authors.initials: IW
authors.lastname: Wainer
authors.forename: W R
authors.initials: WR
authors.lastname: Crom
authors.forename: C P
authors.initials: CP
authors.lastname: McKay
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D005260:Female; D006464:Hemoperfusion; D006801:Humans; D002955:Leucovorin / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D012516:Osteosarcoma / Q000188:drug therapy; D006435:Renal Dialysis; D013763:Tetrahydrofolates / Q000097:blood
chemical_list: D013763:Tetrahydrofolates; D002955:Leucovorin; C005984:5-methyltetrahydrofolate; D008727:Methotrexate