ゾニサミド
ゾニサミドはベンゾイソオキサゾール誘導体であり、スルホンアミド系の抗てんかん薬です。獣医療では主に、犬および猫の難治性特発性てんかんに対する補助療法または単剤療法として使用されます。 * **臨床上のポイント**: フェノバルビタールと比較して肝代謝への負担が少ないため、肝毒性を避ける必要がある患者に好まれることがよくあります。 * 小動物において良好な薬物動態プロファイルを持ち、半減期は犬で約15時間（1日2回投与が可能）、猫で約33時間（1日1回投与が可能）です。 * 人間とは異なり、犬では標準用量において線形薬物動態を示します。
作用機序: The exact mechanism of action is multifactorial and not completely elucidated: * Blocks **voltage-gated sodium channels** and reduces transient inward currents → stabilizes neuronal membranes and suppresses neuronal hypersynchronization. * Inhibits **T-type voltage-gated calcium channels**. * Acts as a weak **carbonic anhydrase inhibitor**. * *Note*: Unlike diazepam or phenobarbital, it does **not** appear to potentiate GABAergic activity.
動物種別の用量
- Epilepsy (anecdotal) · 5 mg/kg PO every 12-24 hours · PO · q12-24h · Most commonly utilized anecdotal dose.
- Refractory to phenobarbital · 5-10 mg/kg PO once daily · PO · q24h · Long half-life makes once daily dosing likely appropriate.
- Epilepsy · 10-20 mg/kg PO once daily · PO · q24h
- Epilepsy · 5-10 mg/kg · PO · q24h · Long-term · Longer half-life in cats allows for once-daily dosing.
- Refractory epilepsy (with phenobarbital) · 5-10 mg/kg PO q12h · PO · q12h · The high end of the dose range is needed when used in combination with phenobarbital due to microsomal enzyme induction.
- Monotherapy · Initially at 5 mg/kg PO twice daily (q12h) · PO · q12h
- Add-on with phenobarbital · 10 mg/kg PO q12h · PO · q12h
- Initial monotherapy · 3-5 mg/kg PO q12h · PO · q12h
- Add-on agent · 10 mg/kg PO q12h · PO · q12h
- Epilepsy · 5-10 mg/kg PO q12h · PO · q12h · Gradual adaptation in dosing is recommended. Reduce phenobarbital doses by 25% at the time of starting zonisamide.
- Epilepsy (monotherapy or adjunctive) · 5-10 mg/kg · PO · q12h · Long-term · Start at 5 mg/kg q12h. If the dog is concurrently receiving phenobarbital, start at 10 mg/kg q12h due to induced metabolism.
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 zonisamide
- Hypersensitivity to sulfonamide drugs
- Pregnancy (known teratogen in dogs)
- Hypersensitivity to sulfonamides
- Severe hepatic impairment
有害事象
- Sedation (usually transient)
- Ataxia
- Inappetence / Anorexia
- Vomiting
- Diarrhea
- Somnolence
- Keratoconjunctivitis sicca (KCS) - theoretical risk due to sulfonamide structure
- Polyarthropathy or blood dyscrasias - theoretical risk due to sulfonamide structure
- Sedation
- Anorexia
- Keratoconjunctivitis sicca (KCS)
- Hepatotoxicity (rare)
- Metabolic acidosis
薬物相互作用
- Phenobarbital · Increases the clearance of zonisamide. Repeated phenobarbital dosing decreases the bioavailability, peak concentrations, half-life, and AUC of zonisamide. This effect can persist up to 10 weeks after phenobarbital discontinuation. Higher zonisamide doses are typically required. · moderate
- Ketoconazole · May inhibit the hepatic metabolism of zonisamide, potentially increasing serum concentrations. · minor
モニタリング
- Clinical efficacy (seizure frequency and severity)
- Serum zonisamide concentrations (suggested therapeutic range in dogs: 10-40 mcg/mL)
- Adverse effects (sedation, ataxia, GI upset)
- Schirmer tear test (monitor for KCS due to sulfonamide structure)
- Serum zonisamide concentrations (therapeutic target typically 10-40 µg/mL)
- Schirmer Tear Test (STT) periodically
- Liver enzymes and bilirubin
- Complete Blood Count (CBC)
過量投与
The LD50 of zonisamide in dogs is reportedly 1 gram/kg. In human overdoses, reported effects include **coma, bradycardia, hypotension, and respiratory depression**. **Treatment**: * GI evacuation if ingestion was recent. * Supportive and symptomatic therapy. * Because of the drug's long half-life, supportive care may be required for several days.
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。