硫鳥嘌呤
硫鳥嘌呤 (Thioguanine, 6-TG) 是一種**嘌呤抗代謝物**抗腫瘤藥物，主要在獸醫學中用作犬貓急性淋巴性或粒細胞性白血病的輔助治療。 **臨床要點：** * 它是一種**細胞週期特異性**藥物，主要作用於 **S期**（DNA合成期）。 * 雖然它與巰嘌呤 (mercaptopurine) 具有廣泛的交叉抗藥性，但其代謝途徑不同（不依賴黃嘌呤氧化酶進行降解），這使得其藥物交互作用與硫唑嘌呤或巰嘌呤有所不同。 * 其治療指數非常狹窄，需要嚴格監測血液學指標。 * 貓對其骨髓抑制作用特別敏感。
作用機制: Thioguanine acts as a false purine base. * **Intracellular Activation:** It is converted by the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** → **thioguanine monophosphate (TGMP)**. * **DNA/RNA Incorporation:** TGMP is further phosphorylated into di- and tri-nucleotides, which are then incorporated into **DNA and RNA**. * **Cytotoxicity:** The insertion of these fraudulent nucleotides disrupts normal nucleic acid synthesis and function, leading to DNA strand breaks and **apoptosis**. * It also causes feedback inhibition of *de novo* purine synthesis, further starving the cancer cells of essential nucleotides.
各物種劑量
- Acute lymphocytic and granulocytic leukemia · 25 mg/m2 PO once daily (q24 hours) for 1-5 days, then every 30 days thereafter as necessary · PO · q24h initially, then q30d · 1-5 days initially, then ongoing · Cats are particularly susceptible to hematologic effects.
- Acute lymphocytic and granulocytic leukemia · 40 mg/m2 PO once daily (q24 hours) for 4-5 days, then every 3rd day thereafter · PO · q24h initially, then q72h · 4-5 days initially, then ongoing · Consultation with a veterinary oncologist is strongly recommended.
- Acute myelogenous leukemias (Protocol 1 & 2) · 50 mg/m2 PO q24-48h · PO · q24-48h · Ongoing · Used as part of a protocol with Cytarabine (100 mg/m2 SC daily for 2-6 days) +/- Doxorubicin (10 mg/m2 IV once a week).
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to thioguanine
- Pregnancy (Category D - teratogenic and mutagenic)
不良反應
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
藥物相互作用
- Hepatotoxic drugs (e.g., halothane, ketoconazole, valproic acid, phenobarbital, primidone) · Increased risk of hepatotoxicity; use concurrently with caution.
- Immunosuppressive drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) · Increased risk of severe infection due to additive immunosuppression.
- Myelosuppressive drugs (e.g., chloramphenicol, flucytosine, amphotericin B, colchicine) · Additive bone marrow depression; extreme caution required.
- Live vaccines · Increased risk of vaccine-induced infection or decreased vaccine efficacy; use with caution or avoid.
監測
- Hemograms (including platelets) initially every 1-2 weeks, then every 1-2 months on maintenance. (Dose reduction of 25% recommended if WBC drops to 5,000-7,000 cells/mm3; discontinue if < 5,000 cells/mm3 until resolved)
- Liver function tests
- Serum amylase (if pancreatitis is suspected)
- Clinical efficacy (remission status)
過量
Toxicity from overdosage can manifest as **acute** (severe gastrointestinal effects like nausea, vomiting, diarrhea) or **delayed** (profound bone marrow depression, hepatotoxicity, severe gastroenteritis). **Treatment:** * If ingestion was recent, use standard protocols to empty the GI tract (emesis/gastric lavage followed by activated charcoal), keeping in mind the risks of handling cytotoxic emesis. * Provide aggressive supportive care (IV fluids, broad-spectrum antibiotics if neutropenic, blood products if severely anemic or thrombocytopenic).
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。