Theoretically required urinary flow during high-dose methotrexate infusion.
The renal excretion of methotrexate (MTX) and its major metabolite 7-hydroxymethotrexate (7-OH-MTX) was analysed in 12 children with malignancies during 52 courses of high-dose methotrexate (H-D-MTX) infusion at dosages ranging from 0.7 to 8.4 g/m2. The peak concentrations of both MTX and 7-OH-MTX exceeded the aqueous solubilities of these compounds at low pH (less than or equal to 6.0). The cumulative MTX excretion in urine was 75%-98% of the administered amount of MTX, and the cumulative 7-OH-MTX excretion in the urine was 3%-15%. The theoretically required urinary flow (TRUF) was estimated as the minimum urine volume needed for complete resolution of MTX and its metabolites in urine. TRUF during MTX infusion from 0 to 6 h and from 6 to 12 h was correlated with the dosage of MTX, and these values were 0.1-1.8 ml/min/m2 at pH 7.0, 0.5-11.1 ml/min/m2 at pH 6.0, and 1.9-42.2 ml/min/m2 at pH 5.0 with dosages of 0.7 to 8.4 g/m2. The value of the theoretically required urinary flow is important to ensure adequate hydration and the optimum alkalinization schedule for massive MTX infusion.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007263:Infusions, Parenteral; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000652:urine*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014563:Urodynamics
C011864:7-hydroxymethotrexate; D008727:Methotrexate