ボリコナゾール
**ボリコナゾール**は、フルコナゾールから派生した広域スペクトルの第2世代トリアゾール系抗真菌薬です。重度で難治性の真菌感染症の治療のために開発されました。 * **広域スペクトル**: 特に**アスペルギルス**、**ブラストミセス**、**クリプトコッカス**をはじめ、カンジダ、ヒストプラズマ、フザリウム属など、さまざまな真菌に対して高い効果を示します。 * **獣医療での臨床使用**: 現在のところ獣医療での臨床経験は限られています。非常に高価であるため広く使用されていませんが、ペットの鳥類は体が小さいため、鳥のアスペルギルス症治療への関心が高まっています。 * **組織移行性**: 多くの動物種で高い経口バイオアベイラビリティを持ち、**中枢神経系 (CNS)**、涙液、滑液に容易に移行するため、全身性および深部の感染症に有用です。 * **猫の感受性**: 猫は重篤な副作用（神経系および全身性）に対して非常に敏感であると考えられています。猫への使用は最終手段としてのみ行うべきです。 * **薬物相互作用**: 他のアゾール系薬剤と同様に、シトクロムP450酵素の強力な阻害剤であり、多くの重要な薬物相互作用を引き起こします。
作用機序: 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.
動物種別の用量
- 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
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
- 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)
有害事象
- 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
薬物相互作用
- 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
モニタリング
- Clinical efficacy (resolution of fungal infection)
- Liver function tests (baseline and periodic)
- Serum electrolytes (potassium, magnesium)
- Neurologic and visual signs (especially in cats)
過量投与
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 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。