伏立康唑
**伏立康唑 (Voriconazole)** 是一種廣效的第二代三唑類抗黴菌藥物，為氟康唑 (fluconazole) 的衍生物，專為治療嚴重且具抗藥性的黴菌感染而開發。 * **廣效性**：對多種黴菌具有高度療效，特別是**麴菌 (Aspergillus)**、**芽生菌 (Blastomyces)** 和 **隱球菌 (Cryptococcus)**，以及念珠菌、組織漿菌和鐮刀菌等。 * **獸醫臨床應用**：目前在獸醫病患中的臨床經驗有限，且藥費極為昂貴，限制了其普及性。然而，由於寵物鳥體型較小，使用此藥治療鳥類麴菌病的關注度正在增加。 * **組織穿透力**：在多種動物體內具有極佳的口服生物可用率，並能輕易穿透進入**中樞神經系統 (CNS)**、淚液和滑液中，對於全身性及深層感染極具價值。 * **貓的敏感性**：貓似乎對此藥的不良反應（神經系統及全身性）極度敏感，因此僅應在無其他選擇的情況下作為最後手段使用。 * **藥物交互作用**：與其他唑類藥物一樣，它是細胞色素 P450 酵素的強效抑制劑，會導致許多顯著的藥物交互作用。
作用機制: Voriconazole exerts its fungistatic (and sometimes fungicidal against *Aspergillus*) effects by inhibiting fungal cell membrane synthesis. * **Primary Mechanism**: It inhibits the cytochrome P-450-dependent enzyme **14-alpha-sterol demethylase** (lanosterol 14-alpha-demethylase) → blocks the conversion of lanosterol to **ergosterol** → depletes ergosterol in the fungal cell wall → alters cell membrane fluidity and permeability, leading to fungal cell death. * **Secondary Mechanism**: Unlike fluconazole, voriconazole also inhibits **24-methylene dehydrolanosterol demethylation** in molds such as *Aspergillus*, which confers its enhanced activity against these specific fungi.
各物種劑量
- Orbital aspergillosis · 10 mg/kg PO once daily. · PO · q24h · Use with extreme caution; significant systemic and neurologic adverse reactions are common.
- Aspergillosis · 3 mg/kg PO q24h · PO · q24h · Higher doses (4-5 mg/kg) are probably necessary to treat infections with Fusarium spp.
- General / Pharmacokinetic study · 18 mg/kg PO q8h for 11 days · PO · q8h · 11 days · Studied in Hispaniolan Amazon parrots; further studies needed for long-term safety.
- Avian aspergillosis · 12.5 mg/kg PO twice daily for 60-90 days or by nebulization as a 1 mg/mL solution for 60 minutes once daily. · PO / Nebulization · q12h / q24h · 60-90 days
- Coccidioidomycosis · 4 mg/kg PO q12h. · PO · q12h
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to voriconazole or other azole antifungals
- Concurrent use with barbiturates, carbamazepine, cisapride, pimozide, quinidine, rifampin, or rifabutin
- Caution in patients with hepatic dysfunction
- Caution in patients with proarrhythmic conditions
- Caution with the IV formulation in patients with decreased renal function (due to accumulation of the SBECD vehicle)
不良反應
- Dogs: Liver enlargement, significant increase in cytochrome P450 hepatic enzymes
- Cats: Azotemia, inappetence, lethargy, weight loss, cutaneous drug reactions, ataxia, hind limb paresis/paraplegia, visual signs (mydriasis, decreased PLR), arrhythmias, hypokalemia
- Humans: Visual disturbances (blurring, spots, wavy lines), rashes, GI effects (nausea, vomiting, diarrhea), hepatotoxicity, hypertension/hypotension, tachycardia, peripheral edema, hypokalemia, hypomagnesemia
- Rare (Humans): Eye hemorrhage, anemia, leukopenia, thrombocytopenia, pancytopenia, QT prolongation, nephrotoxicity
藥物相互作用
- Antidiabetic agents (sulfonylureas) · May increase serum concentrations of these drugs and increase risk for hypoglycemia
- Barbiturates (phenobarbital) · Decreased voriconazole concentrations; concurrent use is contraindicated
- Benzodiazepines · May increase benzodiazepine concentrations
- Calcium-channel blockers (amlodipine, diltiazem, verapamil) · May increase serum concentrations; dosage adjustment may be required
- Carbamazepine · Decreased voriconazole concentrations; concurrent use is contraindicated
- Cisapride · Potential for serious cardiac arrhythmias; concurrent use is contraindicated
- Corticosteroids (prednisolone) · Potentially increased AUC for prednisolone
- Immunosuppressive agents (cyclosporine, tacrolimus) · Increased concentrations; decrease cyclosporine dosage by 50% and tacrolimus dosage by 33% when starting voriconazole
- Methadone · May increase plasma concentrations of R-methadone; monitor for toxicity
- Phenytoin · Can decrease voriconazole concentrations and voriconazole can increase phenytoin concentrations
- Pimozide · Potential for serious cardiac arrhythmias; concurrent use is contraindicated
- Proton-pump inhibitors (omeprazole) · May increase omeprazole (and potentially other PPIs) concentrations
監測
- Clinical efficacy (resolution of fungal infection)
- Liver function tests (baseline and periodic)
- Serum electrolytes (potassium, magnesium)
- Neurologic and visual signs (especially in cats)
過量
The minimum lethal dose in rats and mice is 300 mg/kg (4-7X maintenance dose). * **Clinical Signs**: Increased salivation, mydriasis, ataxia, depression, dyspnea, and seizures. In human pediatric patients, accidental 5X overdoses caused brief photophobia. * **Treatment**: No specific antidote is known. For very large oral overdoses, consider gut emptying (emesis/gastric lavage) followed by close observation and supportive treatment.
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。