メルカプトプリン
**メルカプトプリン（6-MP）**は、チオプリン系の抗悪性腫瘍薬および免疫抑制薬です。 **臨床上のポイントと薬理学:** * **アザチオプリン**と密接な関係があります。アザチオプリンはプロドラッグであり、体内で急速にメルカプトプリンに変換されます。 * 獣医療において第一選択薬として使用されることは稀ですが、**リンパ肉腫**、**急性白血病**、および重度の免疫介在性疾患（**関節リウマチ**や、治療抵抗性の潰瘍性大腸炎/炎症性腸疾患などの難治性自己免疫疾患）の有用な補助療法として機能します。 * 細胞毒性薬であるため、慎重な取り扱いが必要であり、骨髄抑制や肝毒性について患者を厳密に監視する必要があります。
作用機序: Mercaptopurine is an inactive prodrug that requires intracellular activation to exert its cytotoxic and immunosuppressive effects. * Mercaptopurine enters the cell and is converted by the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** → **thioinosinic acid (TIMP)**. * TIMP acts as a **purine antagonist**, inhibiting multiple enzymes required for *de novo* purine synthesis. * False nucleotides are incorporated into DNA and RNA → **inhibition of nucleic acid synthesis** → cell cycle arrest and apoptosis. * It primarily affects rapidly dividing cells, strongly inhibiting **humoral immunity** (B-cell function) and, to a lesser extent, cell-mediated immunity.
動物種別の用量
- As an immunosuppressant in combination with corticosteroids for treating bullous pemphigoid · 2.2 mg/kg · PO · once daily (q24h), then q48h
- For erosive, immune-mediated polyarthritis in combination with corticosteroids · 2 mg/kg · PO · once daily (q24h) for 14-21 days, then q48h (every other day) · 14-21 days initially
- For treatment of immune-mediated diseases or acute lymphocytic and granulocytic leukemias · 50 mg/m2 · PO · once daily (q24h) to effect, then every other day (q48h) or as needed
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 mercaptopurine
- Pregnancy (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
- Allopurinol · Decreases hepatic metabolism of mercaptopurine via xanthine oxidase inhibition. Dose of mercaptopurine must be drastically reduced (to 1/4-1/3 of usual dose) if used concurrently.
- Aminosalicylates (mesalamine, sulfasalazine) · May increase the risk for mercaptopurine toxicity.
- Hepatotoxic drugs (halothane, ketoconazole, valproic acid, phenobarbital, primidone, doxorubicin) · Increased risk of hepatotoxicity; use cautiously together.
- Immunosuppressive drugs (azathioprine, cyclophosphamide, corticosteroids) · Increased risk of severe infection due to additive immunosuppression.
- Myelosuppressive drugs (antineoplastics, chloramphenicol, flucytosine, amphotericin B, colchicine, trimethoprim/sulfa) · Additive bone marrow depression; use with extreme caution.
- Vaccines, live · Increased risk of vaccine-induced infection; use with caution or avoid during therapy.
- Warfarin · Mercaptopurine may reduce the anticoagulant effect of warfarin.
モニタリング
- Hemograms (including platelets): Monitor closely; initially every 1-2 weeks, then every 1-2 months on maintenance therapy. (Note: If WBC drops to 5,000-7,000 cells/mm3, consider reducing dose by 25%. If WBC drops below 5,000 cells/mm3, discontinue until leukopenia resolves).
- Liver function tests (ALT, AST, ALP, Bilirubin)
- Serum amylase (if pancreatitis is suspected)
- Clinical efficacy and signs of toxicity
過量投与
Toxicity may present **acutely** (severe GI effects like vomiting and diarrhea) or be **delayed** (bone marrow depression, hepatotoxicity, gastroenteritis). * **Treatment**: If ingestion was recent, use standard protocols to empty the GI tract (emesis, activated charcoal). Provide aggressive supportive care (IV fluids, antiemetics, broad-spectrum antibiotics if neutropenic, and potentially blood transfusions for severe myelosuppression).
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。