ミトタン
Mitotane
o,p'-DDD (1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene)
別名: Lysodren · o,p'-DDD · CB-313 · NSC-38721 · WR13045 · Lisodren
VetSheet 獣医チームが監修更新日 2026年4月5日エビデンスに基づく獣医学リファレンス
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
動物種別用量
🌎 NA — North America🌍 EU — Europe
犬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A) | 25-50 mg/kg per week | PO | Divided in as many doses as possible weekly | Long-term | 🌎 NA |
| 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 | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol B) | 35-50 mg/kg per week in 2-3 divided doses | PO | Divided weekly | Long-term | 🌎 NA |
| 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) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C) | 50 mg/kg every 7-10 days | PO | Every 7-10 days | Long-term | 🌎 NA |
| Total adrenal ablation (Alternative Protocol D) | 75-100 mg/kg per day for 25 consecutive days, given in 3-4 doses per day with food | PO | Divided q6-8h | 25 days | 🌎 NA |
| Total adrenal ablation (Alternative Protocol E) | 100 mg/kg/day divided twice daily for 30 days | PO | q12h | 30 days | 🌎 NA |
| Palliative medical treatment of adrenal carcinomas or adenomas | 50-75 mg/kg PO in daily divided doses | PO | Divided daily | 10-14 days initially | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction) | 30-50 mg/kg | PO | q24h | to effect (generally 3-10 days) | 🌍 EU |
| Pituitary-dependent hyperadrenocorticism (Maintenance) | 50 mg/kg | PO | q7-14 days | Ongoing | 🌍 EU |
| Adrenal carcinomas | 50-150 mg/kg | PO | q24h | Ongoing | 🌍 EU |
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol A): 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): Adjust based on ACTH stimulation test results.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol B): Goal is basal and post-ACTH cortisol between 1-5 micrograms/dL.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol C): Max 5-7 days prior to ACTH stim test if water consumption cannot be monitored.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C): Dose is highly variable (26-330 mg/kg/week).
- Total adrenal ablation (Alternative Protocol D): Requires lifelong prednisone and mineralocorticoid therapy.
- Total adrenal ablation (Alternative Protocol E): Requires cortisone acetate and fludrocortisone acetate supplementation.
- Palliative medical treatment of adrenal carcinomas or adenomas: May increase to 100 mg/kg/day based on ACTH response. Maintenance is 100-200 mg/kg/week.
- Pituitary-dependent hyperadrenocorticism (Induction): Give with/after food high in fat/oil to improve absorption.
- Pituitary-dependent hyperadrenocorticism (Maintenance): Given in 2-3 divided doses as required. Give with/after food high in fat/oil.
- Adrenal carcinomas: Higher doses may become necessary. Give with/after food high in fat/oil.
猫
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Hyperadrenocorticism | 30-50 mg/kg | PO | q24h | to effect | 🌍 EU |
- Hyperadrenocorticism: Efficacy in cats is very variable, with many showing no response at non-toxic levels. Not recommended.
フェレット
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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 | 🌎 NA |
- Medical treatment of hyperadrenocorticism: Have a compounding pharmacy make 50 mg capsules. Can be coated with Nutrical.
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
概要
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.
安全性・警告
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)
- Diarrhoea
- Acute-onset neurological signs (2-3 weeks post-initiation)
注意事項
Warning: Mitotane should never be administered to animals that are not eating well.
- Diabetes Mellitus: Concurrent diabetes requires close monitoring as insulin requirements may rapidly decrease during initial treatment.
- Organ Dysfunction: Dogs with preexisting renal or hepatic disease should receive the drug with extreme caution and intense monitoring.
- Stress Supplementation: All dogs receiving mitotane therapy must receive additional glucocorticoid supplementation if undergoing physiological stress (e.g., surgery, trauma, acute illness).
- Human Safety: Mitotane is a cytotoxic drug. Caregivers should avoid direct skin contact (wear gloves) and wash hands after administration.
医薬品相互作用
Additive depressant effects may be seen if used concomitantly.
Diabetic dogs receiving insulin may have their insulin requirements rapidly decreased when mitotane therapy is instituted.
Can induce enzymes and reduce the efficacy of mitotane; conversely, mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital.
Has been demonstrated to block the action of mitotane in dogs; an alternate diuretic is recommended.
Increases the hepatic metabolism of mitotane
Increases the hepatic metabolism of mitotane
監視
- 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
- Appetite (daily during induction)
- ACTH stimulation test (to monitor treatment efficacy)
- Blood glucose (in diabetic patients)
- Clinical signs of weakness, vomiting, or neurological changes
薬物動態
吸収
Systemic bioavailability in dogs is poor. Oral absorption is significantly enhanced by giving the drug with food (especially food high in oil/fat content). In humans, ~40% is absorbed with peak serum levels at 3-5 hours.
分布
Distributes to virtually all tissues in the body. It is highly lipophilic, stored in fat, and does not accumulate in the adrenal glands. A small amount may enter the CSF.
代謝
Metabolized in the liver.
消失
Excreted as metabolites in the urine (10%) and bile (15%) within 24 hours of dosing.
過剰投与
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.
製品
製剤
- Tablets
- 500 mg tablet
- 500 mg capsule
ヒト用医薬品
- Mitotane Tablets (scored): 500 mg (Lysodren)
- Lysodren 500 mg tablet
規制ステータス
Available from Europe for animals that have failed trilostane therapy. POM.
POM (Prescription Only Medicine). Used under the cascade.
規制データなし: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Store at room temperature (15-30°C), in tight, light-resistant containers.
飼主向け情報
- 食後に投与: 吸収を良くするため、必ず食後（できれば脂肪や油分を含む食事）すぐにこの薬を投与してください。
- 副作用に注意: この薬の目的はコルチゾール値を下げることですが、下がりすぎることがあります。無気力、脱力感、嘔吐、下痢、突然の食欲不振など、「アジソンクリーゼ」の兆候がないかペットを注意深く観察してください。
- 体調不良時は中止: ペットが食事をとらなくなったり、上記の兆候が見られた場合は、直ちに投薬を中止し、獣医師に連絡してください。ステロイド（プレドニゾンなど）のレスキュー用量の投与を指示される場合があります。
- 安全上の注意: ミトタンは強力な細胞毒性薬です。錠剤を取り扱う際は手袋を着用するか、その後十分に手を洗ってください。子供や他のペットの手の届かない場所に厳重に保管してください。
- ストレス時: 手術、ペットホテルへの預かり、急性の病気などのストレス時には、追加のステロイド薬が必要になる場合があります。獣医師にご相談ください。
VetSheet医薬品リファレンスは獣医専門家の臨床意思決定支援を目的としており、専門的判断または製造業者の最新医薬品情報の代替にはなりません。