• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.1-8
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• 2006

Methotrexate(MTX)는 소아 골육종 환자에서 $12g/m^2$의 고용량을 사용하고 있다. 현재, 소아 골육종 환자에서 신기 능에 따른 고용량 MTX의 임상 약동학은 연구되어 있지 않다. 따라서 본 연구에서는 신기능에 따른 MTX 약동학을 이용하여 구내염을 최소화하는 방법을 제시하고자 하였다. 방법: 환자들의 의무기록지를 후향적 방법으로 검토하였다. 한 병원에서 골육종으로 진단받고, 치료 받은 환자들을 대상으로 정상 신기능군과 비정상 신기능군으로 나누었다. 두 군에 MTX 투여 후 혈중 농도를 각각 비교하였고, 최고 혈중농도도 비교하였다. 혈중 농도와 구내염의 관련성, CL, AUC와 구내염의 상관관계를 분석하였다. 각 군의 terminal half-life, CL, Vss의 평균과 mea residence time(MRT)의 평균을 구하였고, 두 군간 각각을 비교하였다 $({\alpha}=0.05)$. 결과: 환자는 6명이었고, 평가 가능한 총 MTX 투여 회수는 34회였다. MTX 투여 후 최고혈중 농도, 24,48 시간의 혈중농도는 통계적으로 유의성 있는 차이가 있었고, 72,96 시간에서의 농도는 두 군간 유의성이 없었다. 각 군에서 혈중농도와 구내염의 상관관계, 그리고 CL, AUC와 구내염의 상관관계는 발견되지 않았다. Vss를 제외한 모든 파라미터들(terminal half-life, CL, MRT)은 통계적으로 유의성 있는 차이가 있었다. 결론: 비정상 신기능 군에서 MTX 투여 시작 후 24, 48 시간에서의 혈중농도가 더 높고, 변동이 심했다. 또한 MTX의 CL는 감소했고, 혈중농도는 증가하였다. 이러한 사실로 MTX 투여 전 후 혈중 크레아티닌이나 또는 크레아티닌 청소율 모니터링이 필요하다는 것을 알 수 있으며, MTX 투여가 끝난 직후 그리고 그 이후 24 시간 간격으로 혈중 농도를 측정해야함을 알 수 있다.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.581-587
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• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

• Korean Journal of Clinical Pharmacy
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• v.29 no.2
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• pp.101-108
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• 2019

Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received $5g/m^2$ MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or $150{\mu}M$ MTX at 24 hours, and 2 or $5{\mu}M$ at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > $100{\mu}M$ showed higher percentage than group with MTX concentration < $100{\mu}M$ (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at $150{\mu}M$ MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at $2{\mu}M$, p = 0.024 at $5{\mu}M$). Conclusions: MTX concentrations greater than $100{\mu}M$ show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.