小児メトトレキサート大量療法のファルマコキネテイクスと臨床毒性

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High-dose methotrexate (H-DMTX) therapy followed by citrovorum factor rescue is now widely used for the treatment of childhood malignant tumors. To understand pharmacokinetics and toxicity of H-DMTX (50-300 mg/kg), we measured plasma and urine levels of the subject after a total of 170 infusions to 16 children. The samples were obtained 12, 24 and 48hr after the beginning of 6hr infusion. Two phases of plasma MTX disappearance were seen after infusion : the first phase (12-24hr) had a half-life 2.28-3.27 hr and the second phase (24-48hr) 6.96-8.74hr. Significant correlation was obtained between dosage and plasma levels on concentration curve. With the same dose, the younger patients (under 8 years) had low plasma MTX levels, as compared with the older patients (over 13 years). After H-DMTX infusion, severe toxicities such as myelosuppression, abnormal kidney function and stomatitis were observed in 2 cases. We consider that the maximum allowable plasma MTX levels be 10^5M at 24hr and 10^6M at 48hr, on the basis of the finding that the plasma MTX levels in these cases exceeded those levels, respectively, at the same hours. From the beginning of H-DMTX infusion, cumulative urinary excretion in the first 12hr was greater than 50% of the administered dose. Our data suggest that in view of the safety of H-DMTX therapy, monitoring of plasma MTX levels and adequate hydration be important, especially for the older patients.
日本医療薬学会の論文
1984-06-20

小児メトトレキサート大量療法のファルマコキネテイクスと臨床毒性

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