氟康唑
氟康唑（Fluconazole）是一種全身性的**三唑類抗黴菌藥物**。與早期的第一代唑類藥物（如酮康唑）不同，它具有高度親水性，能夠極佳地穿透進入**中樞神經系統 (CSF)**、**眼睛**和**泌尿道**。 > **臨床要點：** 它的吸收不需要酸性胃部環境，因此即使在接受制酸劑治療的病患中，其口服生物利用度也非常穩定。此外，與酮康唑相比，它對哺乳動物細胞色素 P450 酵素的親和力低得多，這意味著它對哺乳動物類固醇激素合成的影響極小，且通常副作用較少。
作用機制: Fluconazole acts by inhibiting the fungal cytochrome P450-dependent enzyme **lanosterol 14-α-demethylase**. Lanosterol → (blocked by fluconazole) → **Ergosterol** This depletion of ergosterol disrupts the synthesis of the fungal cell membrane, increasing its permeability and causing leakage of essential cellular contents. It also impairs the uptake of purine and pyrimidine precursors. Fluconazole is primarily **fungistatic**.
各物種劑量
- Nasal or dermal cryptococcosis · 5-10 mg/kg PO q12-24h, or 10 mg/kg PO q24h · PO · q12-24h · For most infections, 50 mg/cat PO once daily achieves adequate therapeutic levels
- CNS, intraocular, or multisystemic cryptococcosis · 50-100 mg/cat PO or IV q12h · PO/IV · q12h · Often treat neurologic ocular cryptococcosis for at least 12 weeks or 2 weeks after CSF exam shows resolution
- CNS, intraocular or multisystemic mycoses · 50 mg/cat PO once daily (q24h) · PO · q24h
- Cryptococcosis · 50 mg (total dose) PO twice daily · PO · q12h · 1 month beyond resolution of clinical signs
- Cryptococcosis · 50 mg (total dose) PO twice daily · PO · q12h · At least 2 months beyond resolution of clinical signs
- C. immitis infection or Candida bacteremia · Loading dose of 14 mg/kg followed by 5 mg/kg PO once daily · PO · q24h
- Fungal keratitis · 1 mg/kg PO q24h · PO · q24h · Anecdotal reports of successful treatment
- Candidiasis (cockatoos, parrots) · 20 mg/kg PO q24-48h or 10 mg/kg PO q24h · PO · q24-48h · Likely effective for C. albicans. C. galabrata and C. papasilosis may have higher MICs.
- Candidiasis (cockatiels) · 10 mg/kg fluconazole PO suspension and 100 mg/mL fluconazole treated drinking water · PO · Maintained plasma levels above the MIC for most strains of Candida albicans
- Alternate treatment of aspergillosis · 5-10 mg/kg PO once daily · PO · q24h · up to 6 weeks · With or after amphotericin B
- General (Rabbits) · 25-43 mg/kg slow IV q12h · IV · q12h
- Cryptococcosis, candidiasis, systemic mycoses, nasal aspergillosis · 2.5-5 mg/kg PO or IV q12-24h · PO/IV · q12-24h · 56-84 days · Often treat neurologic ocular cryptococcosis for at least 12 weeks or 2 weeks after CSF exam shows resolution
- Fungal meningitis · 5-8 mg/kg PO or IV q12h OR 8-12 mg/kg PO or IV once daily (q24h) · PO/IV · q12h or q24h · 56-84 days
- Urinary candidiasis · 5-10 mg/kg PO q24h · PO · q24h · 21-42 days
- Urinary Candida glabrata infection · 12 mg/kg PO once daily · PO · q24h · 21-42 days
- Cryptococcosis · 5 mg/kg PO once or twice daily · PO · q12h or q24h · At least 2 months beyond resolution of clinical signs
- Blastomycosis · 5 mg/kg PO q12h · PO · q12h · 60 days
- Cryptococcosis · 5-15 mg/kg PO q12-24h · PO · q12-24h · 6-10 months
- Treatment of Malassezia (may be safer than itraconazole or ketoconazole in dogs with hepatic disease) · 5 mg/kg PO once daily · PO · q24h
- Systemic treatment of Malassezia dermatitis · 5 mg/kg PO once daily · PO · q24h
- Recurrent Malassezia dermatitis · 5 mg/kg PO 3 times per week · PO · 3 times per week
- Systemic treatment of Malassezia dermatitis · 2-5 mg/kg PO once daily (q24h) · PO · q24h
- Nasal aspergillosis (alternative to itraconazole or terbinafine) · 2.5-5 mg/kg PO q12h · PO · q12h · 3-6 months · Cure rates up to 60%
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
- Hypersensitivity to fluconazole or other azole antifungals
- Budgerigars (reportedly toxic)
- Pregnant animals
- Lactating animals
不良反應
- Inappetence
- Vomiting
- Diarrhea
- Hepatotoxicity (rare)
- Headache (humans)
- Increased liver enzymes (humans)
- Exfoliative skin disorders (humans)
- Thrombocytopenia (humans)
- Nausea
- Diarrhoea
- Hepatotoxicity
藥物相互作用
- Amphotericin B · May be antagonistic against Aspergillus or Candida; clinical importance unclear
- Buspirone · Plasma concentrations of buspirone may be elevated
- Cisapride · May increase cisapride levels and the possibility for toxicity
- Corticosteroids · May inhibit the metabolism of corticosteroids; potential for increased adverse effects
- Cyclophosphamide · May inhibit the metabolism of cyclophosphamide and its metabolites; potential for increased toxicity
- Cyclosporine · Increases cyclosporine levels; dosage of cyclosporine may need to be decreased by 29%-51%
- Diuretics, Thiazides · Increased fluconazole concentrations
- Fentanyl/Alfentanil · May increase fentanyl levels
- Midazolam · Increased midazolam levels and effects
- NSAIDs · May increase NSAID plasma levels; increased risk for adverse effects
- Quinidine · Increased risk for cardiotoxicity
- Rifampin · May decrease fluconazole efficacy; fluconazole may increase rifampin levels
- Theophylline/Aminophylline · Increased theophylline concentrations
監測
- Clinical efficacy
- Liver function tests (occasional, with long-term therapy)
- Liver enzyme panel (ALT, AST, ALP, Bilirubin) prior to and during prolonged therapy
- Renal function (BUN, Creatinine)
- Resolution of clinical signs of fungal infection
- Therapeutic drug monitoring for concurrent medications like ciclosporin or theophylline
過量
There is limited information on acute toxicity in domestic animals. In rodents, massive overdoses (1-2 g/kg) caused respiratory depression, salivation, lacrimation, urinary incontinence, and cyanosis, leading to death within several days. **Treatment:** If a massive overdose occurs, consider gut emptying (emesis or gastric lavage) if recent, and provide supportive therapy as required. Fluconazole may be removed by hemodialysis or peritoneal dialysis.
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。