氟胞嘧啶
**氟胞嘧啶**（Flucytosine，又稱 5-FC）是一種氟化嘧啶類抗黴菌藥物，主要對**隱球菌 (Cryptococcus)** 和**念珠菌 (Candida)** 具有活性。 **關鍵臨床重點：** * **必須合併治療：** 單獨使用時，黴菌極易產生抗藥性（尤其是隱球菌）。因此幾乎完全與**兩性黴素 B (Amphotericin B)** 或唑類 (Azole) 抗黴菌藥物合併使用以產生協同作用。 * **中樞神經穿透力：** 該藥物能極佳地穿透血腦屏障，在治療中樞神經系統隱球菌症方面具有高度價值。 * **毒性疑慮：** 具有劑量依賴性的骨髓抑制風險。犬隻特別敏感，若治療超過 10-14 天可能會出現嚴重的藥物不良反應。 * **物種差異：** 哺乳動物細胞通常缺乏將氟胞嘧啶轉化為毒性代謝物 (5-氟尿嘧啶) 的酵素，但腸道菌叢或特定物種的代謝（如大鼠）可能導致全身性毒性。
作用機制: Flucytosine acts as a prodrug that exploits specific fungal enzymes: 1. **Cellular Entry:** Flucytosine enters the fungal cell via the enzyme **cytosine permease**. 2. **Conversion to Active Metabolite:** Inside the fungal cell, it is deaminated by **cytosine deaminase** → **5-fluorouracil (5-FU)**. *(Note: Human and most mammalian cells lack this enzyme, providing selective toxicity).* 3. **RNA Inhibition:** 5-FU acts as an antimetabolite, competing with **uracil** → incorporates into fungal RNA → disrupts pyrimidine metabolism and halts protein synthesis. 4. **DNA Inhibition:** 5-FU is also converted to **fluorodeoxyuridylic acid** → potently inhibits **thymidylate synthetase** → halts DNA synthesis and cell division.
各物種劑量
- Cryptococcosis · 30 mg/kg PO q6h or 50 mg/kg PO q8h or 75 mg/kg PO q12h · PO · q6h, q8h, or q12h · 1-9 months · Cats 3.5 kg or greater should receive 250 mg (total) q6-8h. Must be given with a polyene (amphotericin B) or azole antifungal agent.
- Candidiasis · 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h · PO · q6h or q8h · 42 days · Must be given with a polyene or azole antifungal agent.
- Susceptible fungal infections (Psittacines) · 250 mg/kg twice daily as a gavage · PO · q12h · Extended periods · May cause bone marrow toxicity; periodic hematologic assessment is recommended.
- Susceptible fungal infections (Raptors) · 18-30 mg/kg q6h as a gavage · PO · q6h
- Susceptible fungal infections (Psittacines and Mynahs) · 100-250 mg/lb in feed · PO · Continuous · For flock treatment of severe aspergillosis or Candida. Apply to favorite food mix or mixed with mash.
- Susceptible fungal infections (Ratites) · 80-100 mg/kg PO twice daily · PO · q12h
- Cryptococcosis · 50-75 mg/kg PO q8h · PO · q8h · 1-12 months · Must be given with a polyene or azole antifungal agent.
- Candidiasis · 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h · PO · q6h or q8h · 42 days · Must be given with a polyene or azole antifungal agent.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Known hypersensitivity to flucytosine
不良反應
- Gastrointestinal disturbances (nausea, vomiting, diarrhea)
- Dose-dependent bone marrow depression (anemia, leukopenia, thrombocytopenia)
- Cutaneous eruption and rash (primarily on scrotum and nasal planum in dogs)
- Oral ulceration
- Increased hepatic enzymes
- Severe drug reaction in dogs within 10-14 days of treatment
- Aberrant behavior and seizures (reported in cats)
- Toxic epidermal necrolysis (anecdotal in cats)
藥物相互作用
- Amphotericin B · Synergistic antifungal efficacy against Cryptococcus and Candida. However, amphotericin B-induced nephrotoxicity can decrease flucytosine excretion, leading to flucytosine accumulation and enhanced bone marrow toxicity. Dosage adjustments and strict monitoring are required.
監測
- Renal function (BUN, Creatinine, Urinalysis) - at least twice weekly if also receiving amphotericin B
- CBC with platelets (to monitor for bone marrow suppression)
- Hepatic enzymes (at least monthly)
- Serum flucytosine levels (target < 100 mcg/mL) in patients with renal impairment, if available
過量
Specific information regarding flucytosine overdosage in veterinary species is limited. **Management:** * For substantial acute overdoses, standard gastrointestinal decontamination (gut emptying, activated charcoal, and cathartic administration) is recommended unless contraindicated. * Monitor hematologic and renal parameters closely, providing supportive care as needed.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。