アスパラギナーゼ
アスパラギナーゼは、犬や猫の**リンパ系悪性腫瘍**（リンパ腫など）や**白血病**（特に急性リンパ性白血病：ALL）の治療に主に使用される、ユニークな酵素ベースの**抗悪性腫瘍薬**です。 DNAに直接ダメージを与える従来の化学療法薬とは異なり、がん細胞から不可欠な栄養素を奪うことで作用します。骨髄抑制が少なく、消化管粘膜への毒性も低いため、寛解導入療法や骨髄機能がすでに低下している患者の「レスキュー」療法として非常に優れています。 **臨床上のポイント:** 大腸菌由来の巨大な異種タンパク質であるため、過敏症やアナフィラキシーが大きな懸念事項となります。また、免疫系が中和抗体を産生するため、時間の経過とともに有効性が低下することがよくあります。
作用機序: 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.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Patients with a history of anaphylaxis to asparaginase
- Patients with pancreatitis or a history of pancreatitis
有害事象
- Hypersensitivity reactions (vomiting, diarrhea, urticaria, pruritus, dyspnea, hypotension, collapse)
- Hemorrhagic pancreatitis
- Hepatotoxicity
- Coagulation defects
- Hyperglycemia (secondary to altered insulin synthesis)
- Leukopenia (rare)
薬物相互作用
- 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
モニタリング
- 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)
過量投与
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 の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。