ミトタン
ミトタン（別名o,p'-DDD）は、主に獣医学において犬の**下垂体依存性副腎皮質機能亢進症（PDH）**（クッシング症候群）の内科的治療に使用される副腎皮質細胞毒性薬です。殺虫剤DDTと構造的に関連しています。 副腎皮質の標的壊死を引き起こすため、過剰なコルチゾール産生を効果的に減少させます。また、ヒトおよび犬の副腎癌の緩和治療にも使用されます。 **臨床のポイント:** 治療は通常、*導入期*（臨床的エンドポイントに達するまで毎日投与し、過形成した副腎組織を急速に破壊する）と*維持期*（副腎皮質の再増殖を防ぐため週1〜2回投与する）の2つの段階に分けられます。過剰な治療は医原性副腎皮質機能低下症（アジソン病）を引き起こす可能性があるため、厳密なモニタリングが不可欠です。
作用機序: Mitotane acts as a targeted **adrenocortical cytotoxic agent**. * It causes severe, progressive necrosis and atrophy of the **zona fasciculata** and **zona reticularis** of the adrenal gland → drastically reducing the synthesis of glucocorticoids (cortisol). * It relatively spares the **zona glomerulosa**, meaning mineralocorticoid (aldosterone) synthesis is usually unaffected, though clinically significant effects on aldosterone production can occasionally occur. * The exact intracellular mechanism of cytotoxicity is not fully understood, but it is believed to involve metabolic activation within the adrenal mitochondria, leading to irreversible binding to cellular macromolecules and subsequent cell death.
動物種別の用量
- Hyperadrenocorticism · 30-50 mg/kg · PO · q24h · to effect · Efficacy in cats is very variable, with many showing no response at non-toxic levels. Not recommended.
- Medical treatment of hyperadrenocorticism · 50 mg per ferret PO once daily for one week, then 50 mg PO 2-3 times per week · PO · q24h then 2-3 times/week · Long-term · Have a compounding pharmacy make 50 mg capsules. Can be coated with Nutrical.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol A) · 25 mg/kg twice a day, PO with food · PO · q12h · Until clinical endpoints occur (usually 4-9 days) · Reduce food by 1/3 the day before. Stop therapy if water consumption approaches 60 mL/kg/day, appetite reduces, vomiting, listlessness, or diarrhea occurs.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A) · 25-50 mg/kg per week · PO · Divided in as many doses as possible weekly · Long-term · Adjust based on ACTH stimulation test results.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol B) · 30-50 mg/kg/day PO with a meal once daily or divided q12h · PO · q24h or q12h · 7-10 days · Goal is basal and post-ACTH cortisol between 1-5 micrograms/dL.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol B) · 35-50 mg/kg per week in 2-3 divided doses · PO · Divided weekly · Long-term
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol C) · 50 mg/kg divided q12h · PO · q12h · Until water consumption decreases to <100 mL/kg/day or adverse signs observed (usually 3-7 days) · Max 5-7 days prior to ACTH stim test if water consumption cannot be monitored.
投与経路
禁忌
- Known hypersensitivity to mitotane
- Pregnancy (FDA Category C in humans; Class D in veterinary medicine - embryotoxic/teratogenic)
- Patients that are not eating well (should never be administered to anorexic animals)
- Not recommended in cats (trilostane is more effective and mitotane efficacy is highly variable)
有害事象
- Lethargy
- Ataxia
- Weakness
- Anorexia (loss of appetite)
- Vomiting
- Diarrhea
- Neurologic signs (uncommon)
- Liver changes (congestion, centrolobular atrophy, fatty degeneration)
- Iatrogenic hypoadrenocorticism (requiring long-term glucocorticoid/mineralocorticoid replacement in ~5% of dogs)
- Anorexia
- Diarrhoea
- Acute-onset neurological signs (2-3 weeks post-initiation)
- Iatrogenic hypoadrenocorticism
薬物相互作用
- CNS Depressants · Additive depressant effects may be seen if used concomitantly. · moderate
- Insulin · Diabetic dogs receiving insulin may have their insulin requirements rapidly decreased when mitotane therapy is instituted. · major
- Phenobarbital · Can induce enzymes and reduce the efficacy of mitotane; conversely, mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital.
- Spironolactone · Has been demonstrated to block the action of mitotane in dogs; an alternate diuretic is recommended. · major
- Barbiturates · Increases the hepatic metabolism of mitotane · moderate
- Corticosteroids · Increases the hepatic metabolism of mitotane · moderate
モニタリング
- Physical exam and history (especially water consumption, food consumption, and weight)
- ACTH response test (crucial for dose adjustment)
- Serum electrolytes (Na+/K+)
- BUN
- CBC
- Liver enzymes
- Blood glucose
- Appetite (daily during induction)
- ACTH stimulation test (to monitor treatment efficacy)
- Blood glucose (in diabetic patients)
- Clinical signs of weakness, vomiting, or neurological changes
過量投与
Because of the drug's toxicity and very long half-life, acute overdosage should be managed aggressively. * **Decontamination:** Emptying the stomach and administering activated charcoal and a cathartic should be considered after a recent ingestion. * **Monitoring & Treatment:** The patient must be closely monitored. Administer systemic glucocorticoids (e.g., dexamethasone or prednisone) and IV fluids if signs of acute hypoadrenocorticism (Addisonian crisis) develop.
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。