門冬醯胺酶
門冬醯胺酶是一種獨特的酵素類**抗腫瘤藥物**，主要用於獸醫腫瘤學中治療犬貓的**淋巴系統惡性腫瘤**（如淋巴瘤）和**白血病**（特別是急性淋巴細胞白血病 ALL）。 與直接破壞 DNA 的傳統化療藥物不同，它透過剝奪癌細胞的重要營養物質來發揮作用。因為它對骨髓（極少引起骨髓抑制）和胃腸道黏膜的毒性較小，所以當病患骨髓功能已經受損時，它是誘導方案或「救援」治療的絕佳選擇。 **臨床重點：** 由於它是一種大型外來蛋白質（源自大腸桿菌），過敏反應/過敏性休克是一個主要的臨床問題，且其療效會因病患免疫系統產生中和抗體而隨時間下降。
作用機制: Normal cells can synthesize their own asparagine using the enzyme **asparagine synthetase**. However, many lymphoid malignant cells lack this enzyme and rely entirely on exogenous asparagine from the bloodstream for protein and DNA synthesis. Asparaginase is an enzyme that circulates in the intravascular space and catalyzes the breakdown of circulating asparagine: **L-asparagine** + H2O → (via **L-asparaginase**) → **Aspartic acid** + **Ammonia** By rapidly depleting circulating asparagine, the drug halts protein synthesis in the tumor cells, leading to apoptosis. The antineoplastic activity is greatest during the post-mitotic (**G1**) phase of the cell cycle.
各物種劑量
- Lymphoid malignancies / Leukemia · 400 Units/kg or 10,000 Units/m2 IM or SC, with a maximum dose of 10,000 Units per patient · IM/SC · Protocol dependent · Protocol dependent · Many oncologists recommend administering diphenhydramine at 2 mg/kg SC 30 minutes prior to administration.
- Treatment of lymphoid malignancies · 10,000 IU/m2 or 400 IU/kg · IM/SC · q7d or less frequently · As per chemotherapy protocol · See specialist texts for chemotherapy protocols and conversion of body weight to body surface area.
- Lymphoid malignancies / Leukemia · 400 Units/kg or 10,000 Units/m2 IM or SC, with a maximum dose of 10,000 Units per patient · IM/SC · Protocol dependent · Protocol dependent · Many oncologists recommend administering diphenhydramine at 1 mg/kg SC 30 minutes prior to administration.
- Treatment of lymphoid malignancies · 10,000 IU/m2 or 400 IU/kg · IM/SC · q7d or less frequently · As per chemotherapy protocol · See specialist texts for chemotherapy protocols and conversion of body weight to body surface area.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Patients with a history of anaphylaxis to asparaginase
- Patients with pancreatitis or a history of pancreatitis
不良反應
- Hypersensitivity reactions (vomiting, diarrhea, urticaria, pruritus, dyspnea, hypotension, collapse)
- Hemorrhagic pancreatitis
- Hepatotoxicity
- Coagulation defects
- Hyperglycemia (secondary to altered insulin synthesis)
- Leukopenia (rare)
藥物相互作用
- Methotrexate · Asparaginase may reduce methotrexate effectiveness against tumor cells until serum asparagine levels return to normal.
- Prednisone · Concurrent use may increase the risk for hyperglycemia.
- Vincristine · Increased toxicity (neuropathy and erythropoiesis disruption) and myelosuppression may occur. Some oncologists recommend separating the dosing by a few days to a week. · major
監測
- Hepatic function
- Renal function (BUN may be increased by drug action)
- Pancreatic function (blood glucose, amylase)
- Hematopoietic function
- Patient observation for hypersensitivity during and immediately after administration
- Serum ammonia (may be increased)
過量
In dogs, the maximally tolerated dose is 10,000 IU/kg and the lethal dose is 50,000 IU/kg. Overdosage is expected to cause severe toxicity secondary to protein synthesis alteration (pancreatitis, hepatotoxicity, coagulopathy). Treatment is supportive.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。