メチマゾール
**メチマゾール**はチオイミダゾール誘導体の抗甲状腺薬であり、北米において**猫の甲状腺機能亢進症に対する内科的治療のゴールドスタンダード**とされています。 主な臨床的ポイント： - **主な用途**: 猫の甲状腺機能亢進症の管理。血中の甲状腺ホルモン濃度を効果的に低下させ、体重減少、多食、頻脈などの臨床症状を改善します。 - **代替投与経路**: 経口投与が困難な猫に対しては、耳介内側に塗布する**経皮吸収ゲル（PLOゲル）**として調剤することが可能であり、良好な臨床効果（経口よりはやや劣る）を示し、胃腸の副作用を軽減できる可能性があります。 - **治験的用途**: 犬において、シスプラチン誘発性腎毒性を予防するための静脈内注射として使用された報告があります。 - **臨床のポイント**: メチマゾールは甲状腺機能亢進症を管理するものであり、*完治させるものではありません*。根治的治療（放射性ヨウ素治療や甲状腺摘出術）を行わない限り、生涯にわたる毎日の投薬が必要です。
作用機序: Methimazole acts directly within the thyroid gland to block the synthesis of thyroid hormones (T3 and T4). - **Mechanism**: It actively inhibits the enzyme **thyroid peroxidase (TPO)**. - **Pathway**: Inhibition of TPO → prevents the oxidation of iodide to iodine → blocks the incorporation of iodine into tyrosyl residues of thyroglobulin → inhibits the coupling of iodinated tyrosyl residues to form iodothyronine (T3 and T4). - **Important Note**: Methimazole has **no effect** on the release or activity of thyroid hormones that are already formed and stored, or those currently in systemic circulation. This accounts for the **1 to 3 week lag time** often seen before serum T4 levels significantly decrease and clinical improvement is noted.
動物種別の用量
- Hyperthyroidism · The starting dose is 2.5 mg administered every 12 hours. Following 3 weeks of treatment, the dose should be titrated to effect based on individual serum total T4 (TT4) levels and clinical response. Dose adjustments should be made in 2.5 mg increments. The maximum total dosage is 20 mg per day divided, not to exceed 10 mg as a single administration. · PO · q12h · Lifelong
- Hyperthyroidism (cats with azotemia or for clients declining radioiodine) · 1.25-5 mg per cat twice daily (start at lower end. · PO · q12h · Lifelong
- Hyperthyroidism (transdermal administration) · 2.5 mg to inner pinna q12h. · topical · q12h · Lifelong · Methimazole (50 mg/mL; 5 mg/0.1 mL) in PLO. Person applying should wear gloves or finger cots. Somewhat lower efficacy than PO (67% vs 82% euthyroid at 4 weeks). Lower incidence of GI effects.
- Hyperthyroidism (gradual titration) · Initially, 2.5 mg (total dose) PO once a day for 2 weeks. If adverse reactions not noted... increase to 2.5 mg PO twice daily and the same parameters are checked in another 2 weeks. The dosage should then be increased every 2 weeks by 2.5 mg per day until serum T4 is between 13 and 26 nmol/L or adverse effects develop. · PO · q24h initially, then q12h · Lifelong
- Hyperthyroidism (based on renal status) · If no signs of renal insufficiency/failure, begin at 5 mg (total dose) PO twice daily in cases with severely increased T4 levels. If renal insufficiency present (or not sure), start at 2.5 mg twice daily. If azotemia and overt renal failure, start at 1.25 mg twice a day. · PO · q12h · Lifelong · Monitor in 1-2 weeks (T4, CBC with platelet count, renal blood parameters, urinalysis).
- Hyperthyroidism · 2.5 mg/cat · PO · q12h · Long-term · 2 to 3 weeks of treatment generally needed to establish euthyroidism. Adjust dose based on T4 monitoring.
投与経路
禁忌
- Hypersensitivity to methimazole, carbimazole, or polyethylene glycol
- Autoimmune disease
- Primary liver disease
- Renal failure
- Hematologic disorders or coagulopathies
- Pregnant or lactating queens
- Pregnant queens
- Lactating queens
- Animals with known hypersensitivity to thiamazole or carbimazole
有害事象
- Vomiting
- Anorexia
- Depression/Lethargy
- Transient eosinophilia, leukopenia, and lymphocytosis
- Self-induced facial excoriations (pruritus)
- Bleeding/Coagulopathies
- Hepatopathy
- Thrombocytopenia
- Agranulocytosis
- Positive direct antiglobulin test (DAT)
- Positive ANA (in chronic use >6 months)
- Acquired myasthenia gravis (rare)
- Inappetence / Anorexia
- Jaundice / Hepatopathy
- Cytopenias (thrombocytopenia, leukopenia, anemia)
- Immune-mediated diseases (e.g., myasthenia gravis)
薬物相互作用
- Benzimidazole antiparasitics · Methimazole can reduce hepatic oxidation of benzimidazoles and increase blood levels.
- Beta-blockers · A reduction in dose may be needed when the patient becomes euthyroid.
- Bupropion · Potential for increased risk for hepatotoxicity; increased monitoring (LFT's) necessary.
- Digoxin · Methimazole may decrease digoxin efficacy, but a reduction in dose may be needed when the patient becomes euthyroid.
- Phenobarbital · Concurrent use of phenobarbital may reduce the clinical effectiveness of methimazole. · moderate
- Theophylline · A reduction in dose may be needed when the patient becomes euthyroid.
- Warfarin · Anticoagulants may be potentiated by methimazole. Increased monitoring of anticoagulant effect is warranted.
- Benzimidazoles · Reduce hepatic oxidation and may lead to increased circulating thiamazole concentrations · moderate
- Iodine-131 (Radioiodine) · Thiamazole interferes with radioiodine uptake; must be discontinued prior to I-131 treatment · major
- Low-iodine prescription diets · Concurrent use is not recommended as it confounds dietary management and iodine restriction · moderate
モニタリング
- Baseline and every 2-3 weeks for the first 3 months: CBC, platelet count, Serum T4
- Liver function tests and ANA if indicated by symptomatology
- After stabilization (at least 3 months): T4 at 3-6 month intervals
- Renal parameters (BUN, Creatinine, USG) to monitor for unmasked kidney disease
- Cats receiving >10 mg/day require more frequent monitoring
- Serum total T4 (measure 4-6 hours post-pill)
- Haematology (CBC for cytopenias)
- Biochemistry (BUN, Creatinine, Liver enzymes)
- Monitor at 3, 6, 10, and 20 weeks after starting therapy, and every 3 months thereafter
過量投与
Acute toxicity from overdosage mirrors severe adverse effects: **agranulocytosis, hepatopathy, and thrombocytopenia** are the most serious concerns. **Treatment**: - Follow standard protocols for oral ingestion (empty stomach if not contraindicated, administer activated charcoal). - Provide symptomatic and supportive care (e.g., IV fluids, hepatoprotectants, broad-spectrum antibiotics if neutropenic).
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。