Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue".
We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CV. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.
D000293:Adolescent; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy*; D002648:Child; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy*; D010649:Phenylalanine / Q000097:blood*; D013997:Time Factors; D014443:Tyrosine / Q000097:blood*
D014443:Tyrosine; D010649:Phenylalanine; D002955:Leucovorin; D008727:Methotrexate