トリロスタン
トリロスタンは合成ステロイドアナログであり、犬の下垂体依存性および副腎依存性副腎皮質機能亢進症（クッシング症候群）の管理における現在の**標準治療薬**です。 副腎皮質の壊死を引き起こすミトタンなどの古い治療法とは異なり、トリロスタンはステロイド産生を可逆的に阻害します。これにより、一般的に安全で予測可能ですが、医原性副腎皮質機能低下症（アジソン病）を防ぐための慎重なモニタリングが依然として必要です。 **主な臨床用途:** * **犬:** 下垂体依存性および副腎依存性クッシング症候群、脱毛症X（特にポメラニアンやアラスカン・マラミュート）。 * **猫:** 猫の下垂体依存性クッシング症候群（適応外使用）。 * **馬:** 馬のクッシング症候群 / 下垂体中葉機能障害（PPID）（適応外使用。ただし、PPIDの第一選択薬としてはペルゴリドが一般的です）。 > **臨床のポイント:** 副腎腫瘍を持つ犬に使用する場合、トリロスタンはクッシング症候群の臨床症状をコントロールしますが、腫瘍を縮小させることは**ありません**。実際、治療中にネガティブフィードバックの喪失により副腎が代償性肥大を起こし、サイズが大きくなることがあります。
作用機序: Trilostane acts as a competitive, reversible, and dose-dependent inhibitor of the enzyme **3-beta hydroxysteroid dehydrogenase (3β-HSD)**. * **Pathway Blockade:** Pregnenolone → **[3β-HSD Blocked]** → Progesterone * By blocking this crucial early step in the adrenal steroidogenesis pathway, trilostane effectively reduces the downstream synthesis of **cortisol**, **aldosterone**, and **adrenal androgens**. * Because the inhibition is competitive and reversible, the suppressive effects on cortisol production wane within 10 to 20 hours, necessitating daily or twice-daily dosing.
動物種別の用量
- Hyperadrenocorticism · 7 mg/kg/day divided and given twice daily · PO · q12h · Doses of up to 60 mg per cat per day have been used.
- Hyperadrenocorticism · 15 mg (total dose) PO once daily to 60 mg (total dose) PO q12h · PO · q24h to q12h · Titrate dose with ACTH stimulation tests. Cats typically remain diabetic despite clinical improvement.
- Hyperadrenocorticism · 10-30 mg/cat p.o. q12-24h · PO · q12h to q24h · Lifelong · Give with food.
- Equine Cushing's syndrome · 0.4-1 mg/kg (total dose 120-240 mg) PO once daily · PO · q24h
- Hyperadrenocorticism (HAC) - Label Dose · 2.2-6.7 mg/kg PO once a day with food · PO · q24h · Adjust dose based on ACTH stimulation test 10-14 days post-initiation. May require twice daily dosing if clinical signs are not controlled for the full day.
- Hyperadrenocorticism (HAC) - Alternative Protocol · 2-10 mg/kg PO once daily · PO · q24h · Doses of up to 50 mg/kg/day divided twice daily have been given. Adjust based on ACTH stim test 4-6 hours post-dose.
- Hyperadrenocorticism (HAC) - Low Dose Protocol · 1 mg/kg PO once daily · PO · q24h · Recheck in 1 week. Adjust based on clinical response, UCCR, and ACTH stimulation test.
- Alopecia X (Alaskan Malamutes) · 3-3.6 mg/kg PO twice a day · PO · q12h · 4-6 months
投与経路
禁忌
- Hypersensitivity to trilostane
- Pregnancy (reduces progesterone synthesis)
- Use with caution in patients with renal impairment
- Use with caution in patients with hepatic impairment
- Renal insufficiency
- Hepatic insufficiency
有害事象
- Lethargy
- Inappetence
- Vomiting
- Diarrhea
- Mild electrolyte abnormalities (hyponatremia, hyperkalemia)
- Iatrogenic hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis (rare but potentially fatal)
- Mild gastrointestinal signs
- Mild increases in serum potassium, bilirubin, and calcium
- Clinical hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis
- Adrenal hyperplasia (with prolonged treatment)
- Prolonged adrenal suppression after drug withdrawal
薬物相互作用
- ACE Inhibitors (e.g., benazepril, enalapril) · Could increase risk for hyperkalemia
- Aminoglutethimide · May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Ketoconazole · May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Mitotane · May potentiate the effects of trilostane and lead to hypoadrenocorticism · major
- Potassium-sparing diuretics (e.g., spironolactone) · Could increase risk for hyperkalemia
- Potassium supplements / High potassium foods · Could increase risk for hyperkalemia
- Itraconazole · Concurrent suppression of adrenal function · moderate
モニタリング
- Clinical signs (water intake, urination, appetite, energy level)
- Adverse effects (vomiting, diarrhea, lethargy)
- Serum electrolytes (Sodium and Potassium)
- Urinalysis (Specific gravity, glucose, urine cortisol:creatinine ratio [UCCR])
- ACTH stimulation tests (conducted 4-6 hours post-pill)
- Clinical signs (water intake, urination, appetite, hair coat)
- ACTH stimulation test (3 hours post-pill)
- Pre-pill baseline cortisol
- Serum electrolytes (potassium, calcium)
- Liver parameters (bilirubin)
過量投与
Acute overdoses are unlikely to be life-threatening, and severe clinical signs are not typically expected immediately. * **Monitoring:** Assess blood pressure, hydration status, and electrolyte balance (Na/K). * **Treatment:** If the animal is stressed or showing signs of hypoadrenocorticism, consider administering exogenous corticosteroids short-term. * Because the drug's effects are relatively short-lived, monitoring of uncomplicated patients is usually only required for a few days post-ingestion.
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。