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題名 | 低劑量Methotrexate之安全性評估=Low Dose of Methotrexate Safety Assessment |
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作者姓名(中文) | 楊璦瑜; 郭震羣; | 書刊名 | 藥學雜誌 |
卷期 | 32:4=129 2016.12[民105.12] |
頁次 | 頁37-41 |
分類號 | 418.29 |
關鍵詞 | 安全性; 慢性腎臟疾病; Methotrexate; |
語文 | 中文(Chinese) |
中文摘要 | 低劑量的 Methotrexate (MTX) 具有抗發炎跟免疫抑制的作用。因為療效跟安全 性,是目前廣泛使用的疾病修飾抗風濕病藥物。MTX 是葉酸拮抗劑,經由抑制二氫 葉酸還原酶,而抑制 DNA、RNA 的合成。MTX 有幾個潛在的副作用,包括急性肺 炎、肝毒性和骨髓抑制,是非常嚴重的,甚至會危及生命。 MTX 的藥物動力學是多變和無法預知的,可以口服、肌肉、皮下注射,吸收率 相似。口服的生體可用率為20-95%,個體差異甚大。肝臟代謝後、經由腎臟排泄, 若腎臟功能缺損可能導致巨大的分佈體積和白蛋白結合異常,影響體內藥物濃度。濃 度增加可能造成藥物毒性,產生嚴重不良反應。MTX 毒性是治療終止的主要原因。 低劑量使用也需要謹慎的評估病人的血液情形、肝、腎功能。密切的監測相關危 險因子,考量腎功能作適當的劑量調整以提升藥物治療的安全性。 |
英文摘要 | Methotrexate (MTX), when used in low doses, has anti-inflammatory and immunosuppressive action. Because of its efficacy and safety, low dose methotrexate is now widely used disease-modifying anti-rheumatic drugs. Methotrexate is a antifolate analogues that inhibits dihydrofolate reductase, inhibiting the DNA and RNA synthesis. MTX has several potential side effects, including acute pneumonitis, hepatotoxicity and bone marrow suppression, which are very serious and sometimes life-threatening. The pharmacokinetics of MTX is variable and unpredictable. It can be given orally, intramuscularly or by subcutaneous injection, with similar rates of absorption, regardless of the route of administration. The bioavailability of oral methotrexate varies considerably between individuals, and in general is in the range of 20~95%. Renal clearance is the principal mechanism of elimination of methotrexate, and patients with renal failure have decreased clearance of the drug. Even with low dosing, this can lead to ineffective renal clearance because of great volume distribution and poor binding to serum albumin. Ineffective renal clearance of the drug would lead to higher plasma levels and a prolonged half-life, even induced serious adverse reaction. MTX toxicity is the main reason for treatment discontinuation. During low dose MTX treatment, we also need prudential monitoring full blood counts, and renal function, and liver function. Close monitoring of associated risk factors, appropriate dosage adjustment in renal insufficiency to improve drug safety. |
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