フルシトシン
**フルシトシン**（5-FCとも呼ばれる）は、主に**クリプトコッカス**および**カンジダ**株に対して活性を示すフッ素化ピリミジン系抗真菌薬です。 **臨床上の重要なポイント：** * **併用療法の必須性：** 単独療法として使用すると、真菌の耐性が急速に発現します（特にクリプトコッカス）。そのため、ほぼ例外なく**アムホテリシンB**またはアゾール系抗真菌薬と相乗的に併用されます。 * **中枢神経系への移行性：** 血液脳関門を非常によく通過するため、中枢神経系のクリプトコッカス症の治療に極めて有用です。 * **毒性に関する懸念：** 用量依存性の骨髄抑制のリスクがあります。犬は特に敏感であり、10〜14日以上治療すると重篤な薬物反応を起こす可能性があります。 * **種差：** 哺乳類の細胞は一般に、フルシトシンを毒性代謝物（5-フルオロウラシル）に変換するために必要な酵素を欠いていますが、腸内細菌叢や特定の種の代謝（ラットなど）により全身毒性が生じる可能性があります。
作用機序: 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.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Known hypersensitivity to flucytosine
有害事象
- 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)
薬物相互作用
- 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.
モニタリング
- 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
過量投与
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 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。