Methotrexate clearance and clinical toxicity in osteosarcoma following high-dose methotrexate therapy. 1989

M P Iqbal, and M Khursheed, and N Mahboobali

Two patients with osteogenic sarcoma were treated with high-dose methotrexate (MTX) followed by leucovorin 'rescue'. Profiles of MTX clearance from plasma and erythrocytes were obtained. Clearance of the drug from plasma during the first 36 hours appears to be biphasic with the first phase of elimination of the drug being appreciably more rapid than the second phase. The drug had also incorporated into the bone marrow precursor cells and reappeared after a few days in the circulating mature erythrocytes which may later serve as a slow-changing compartment for MTX. Nonspecific binding of the drug to plasma proteins may have been one of the causes of delayed clearance of plasma MTX observed in one of the patients. However, delayed clearance does not appear to correlate with the severity of clinical toxicity which was found to be more pronounced in a patient with a better clearance of the drug. Our results support the more recent concept that enhanced clinical toxicity may not be predictable by monitoring plasma MTX alone.

UI MeSH Term Description Entries
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012516 Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed) Sarcoma, Osteogenic,Osteogenic Sarcoma,Osteosarcoma Tumor,Osteogenic Sarcomas,Osteosarcoma Tumors,Osteosarcomas,Sarcomas, Osteogenic,Tumor, Osteosarcoma,Tumors, Osteosarcoma

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