チオグアニン
チオグアニン (6-TG) は、主に犬や猫の急性リンパ性または顆粒球性白血病の補助治療として使用される**プリン代謝拮抗剤**の抗悪性腫瘍薬です。 **臨床上のポイント：** * **細胞周期特異的**な薬剤であり、主に**S期**（DNA合成期）に作用します。 * メルカプトプリンと広範な交差耐性を示しますが、代謝経路が異なります（分解にキサンチンオキシダーゼを必要としないため、アザチオプリンやメルカプトプリンとは相互作用のプロファイルが異なります）。 * 治療指数が非常に狭いため、血液学的パラメータの厳密なモニタリングが必要です。 * 猫は特に骨髄抑制作用に対して敏感です。
作用機序: 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.
動物種別の用量
- 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).
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
- Hypersensitivity to thioguanine
- Pregnancy (Category D - teratogenic and mutagenic)
有害事象
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
薬物相互作用
- 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.
モニタリング
- 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)
過量投与
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 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。