트릴로스탄

부신 스테로이드 합성 억제제

트릴로스탄은 합성 스테로이드 유사체로, 반려견의 뇌하수체 의존성 및 부신 의존성 부신피질기능항진증(쿠싱 증후군) 관리의 현재 **표준 치료제**입니다. 부신 피질의 괴사를 유발하는 미토탄과 같은 과거의 치료법과 달리, 트릴로스탄은 스테로이드 생성을 가역적으로 억제합니다. 이로 인해 일반적으로 더 안전하고 예측 가능하지만, 의인성 부신피질기능저하증(애디슨병)을 예방하기 위해 세심한 모니터링이 여전히 필요합니다. **주요 임상 용도:** * **개:** 뇌하수체 의존성 및 부신 의존성 쿠싱 증후군; 탈모증 X(특히 포메라니안 및 알래스칸 말라뮤트). * **고양이:** 고양이 뇌하수체 의존성 쿠싱 증후군(오프라벨). * **말:** 말 쿠싱 증후군 / 뇌하수체 중엽 기능 장애(PPID)(오프라벨, PPID의 1차 치료제로는 주로 페르골리드가 사용됨). > **임상 팁:** 부신 종양이 있는 개에게 사용할 경우, 트릴로스탄은 쿠싱 증후군의 임상 증상을 조절하지만 종양의 크기를 줄이지는 **않습니다**. 실제로 치료 중 음성 피드백 상실로 인해 부신이 보상성 비대를 겪으며 크기가 커질 수 있습니다.

작용 기전: 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.

동물 종별 용량

Cats

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.

Horses

Equine Cushing's syndrome · 0.4-1 mg/kg (total dose 120-240 mg) PO once daily · PO · q24h

Dogs

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

투여 경로

금기

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

이상반응

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

약물 상호작용

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

모니터링

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)

과용량

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.

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