メタドン
Methadone
Methadone hydrochloride
別名: Dolophine · Methadose · Diskets · Comfortan · Synthadon · Amidine HCl · amidone HCl · methadoni hydrochloridum · Phenadone · Methadone hydrochloride · Metadona
VetSheet 獣医チームが監修更新日 2026年4月5日エビデンスに基づく獣医学リファレンス
監査済み v13 用量エビデンス
確認済み・計算対象外のエビデンス確認済み・計算対象外のエビデンス (1)
エビデンス表示のみ（自動計算対象外）
Anesthesia premedication (extra-label)
Anesthesia premedication (extra-label): Methadone 0.1 – 0.6 mg/kg IV, IM, or SC 70,74
必ず考慮する臨床コンテキスト (2)
- NOTE: All listed dosages are based on the methadone HCl salt formulation (10 mg methadone HCl is equivalent to ≈8.9 mg of methadone). Most products are labeled with methadone HCl strength but check before administering to patients.
- Methadone injection should be stored at room temperature of 20°C to 25°C (68°F-77°F) and protected from light. Store vials in the manufacturer’s carton until ready for use.
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
概要
メタドンは合成の強力なμ-オピオイド受容体作動薬であり、主に犬や猫の麻酔前投薬や鎮痛薬として使用されます。モルヒネと比較して、静脈内投与時のヒスタミン遊離が有意に少なく、嘔吐や過度の鎮静を引き起こしにくい特徴があります。
臨床上のポイントと薬理学的利点:
- トリプルアクション: 多くの従来のオピオイドとは異なり、メタドンはμ-作動薬であるだけでなく、非競合的NMDA受容体拮抗薬およびモノアミン（セロトニンおよびノルアドレナリン）再取り込み阻害薬でもあります。
- 神経障害性疼痛: NMDA拮抗作用があるため、難治性疼痛、神経障害性疼痛の治療、および中枢感作（ワインドアップ現象）の予防に特に有用です。
- バイオアベイラビリティ: 犬における経口バイオアベイラビリティは非常に低いため、獣医療では非経口投与（IV、IM、SC）が標準的な投与経路となります。
- 規制: 人間における乱用のリスクが高いため、スケジュールII（C-II）の規制薬物に指定されています。
作用機序
Methadone provides analgesia through a unique, multi-modal mechanism of action:
- Mu-Opioid Receptor (MOR) Agonism: Binds to MORs in the central nervous system → inhibits adenylyl cyclase → decreases cAMP → promotes opening of inward-rectifying potassium channels and closing of voltage-gated calcium channels → hyperpolarization of neurons and decreased release of nociceptive neurotransmitters (e.g., Substance P, glutamate).
- NMDA Receptor Antagonism: Acts as a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor → blocks glutamate binding → reduces central sensitization and hyperalgesia.
- Monoamine Reuptake Inhibition: Inhibits the presynaptic reuptake of serotonin (5-HT) and norepinephrine (NE) → increases monoamine concentrations in the synaptic cleft → enhances descending inhibitory pain pathways in the spinal cord.
安全性・警告
禁忌
- Late-term pregnancy (due to risks of respiratory depression and stillbirths)
- Known hypersensitivity to methadone
- No specific contraindications available in the monograph, but use with caution in patients with severe respiratory compromise or hepatic impairment.
有害事象
- Panting
- Whining or vocalization
- Defecation
- Constipation
- Bradycardia
- Pronounced CNS excitement (in horses at IV doses ≥ 0.1 mg/kg)
- Respiratory depression (primarily under general anaesthesia)
- Transient excitation (when given IV)
- Salivation (when given via oral transmucosal route in cats due to preservatives)
- Constriction of gastrointestinal sphincters (e.g., pyloric sphincter)
- Reduction in gastrointestinal motility (with prolonged use)
- Neonatal sedation (crosses the placenta)
注意事項
All opiates should be used with caution in patients with heart failure, hypertension, head injuries, elevated CSF pressures, and in geriatric or severely debilitated patients.
Note: Methadone can increase plasma amylase and lipase values up to 24 hours following administration due to increased biliary tract pressure.
医薬品相互作用
May increase risks for arrhythmias
Potentiates sedative and analgesic effects; combination with medetomidine may cause severe hypoxemia in dogs breathing room air
May increase methadone levels in humans (does not appear to be true for dogs)
May increase risks for arrhythmias
May cause increased CNS or respiratory depression
May increase potential for electrolyte abnormalities
Opiates may decrease diuretic efficacy in CHF patients
May inhibit metabolism of methadone and increase levels in humans (does not appear to be true for dogs)
Potential for severe CNS/behavioral reactions; concomitant use should be avoided
Methadone may enhance neuromuscular blockade
May decrease methadone levels in humans (probably does not affect dogs)
May decrease methadone levels in humans (probably does not affect dogs)
May increase methadone levels
May decrease methadone levels in humans (probably does not affect dogs)
Methadone may exacerbate the effects of tricyclic antidepressants
Opiates may potentiate anticoagulant activity
Methadone may increase zidovudine levels
Increased CNS or respiratory depression
監視
- Analgesic or preanesthetic efficacy
- Respiratory rate and depth (monitor for respiratory depression, especially at higher doses)
- Heart rate (bradycardia)
- CNS depression or excitation
- Respiratory rate and depth (especially under general anaesthesia)
- Pain scores (due to individual variation in response)
- Level of sedation
- Gastrointestinal motility (with prolonged use)
薬物動態
半減期
吸収
In dogs, methadone has poor oral bioavailability (not significantly affected by ketoconazole or omeprazole). Subcutaneous bioavailability is ~80% with peak levels around 1 hour. In horses, orally administered methadone is well absorbed but rapidly eliminated.
分布
Highly lipid-soluble and widely distributed. In humans, it is extensively bound to plasma proteins (60-90%).
代謝
Hepatic. Unlike in humans, CYP3A does not appear to be a major metabolic pathway for methadone biotransformation in dogs. Metabolites are inactive.
消失
In dogs, clearance is about 25-30 mL/kg/min.
過剰投与
Overdosage may produce profound respiratory and/or CNS depression in most species. Newborns are particularly susceptible. Other toxic effects include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia.
Treatment:
- Naloxone is the reversal agent of choice for treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated because naloxone's effects might diminish before sub-toxic levels of methadone are attained.
- Mechanical respiratory support should be considered in severe cases.
- Dialysis, charcoal hemoperfusion, or forced diuresis do not appear to be beneficial.
製品
製剤
- Injection
- Oral tablets
- Dispersible tablets
- Oral solution/liquid concentrate
- Injectable: 10 mg/ml solution (including generic preservative-free preparations)
- Oral: 10 mg tablets
動物用医薬品
- Comfortan 10 mg/ml solution for injection
- Synthadon 10 mg/ml solution for injection
ヒト用医薬品
- Methadone HCl Injection: 10 mg/mL
- Methadone HCl Oral Tablets: 5 mg & 10 mg
- Methadone HCl Dispersible Tablets: 40 mg
- Methadone HCl Oral Solution/Liquid Concentrate: 1 mg/mL, 2 mg/mL & 10 mg/mL
- Generic methadone 10 mg tablets
規制ステータス
Authorized veterinary preparations available.
Subject to strict safe custody and register requirements.
規制データなし: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Store at room temperature and protect from light. Methadone injection is reportedly stable when mixed in a syringe with acepromazine, but is NOT compatible with pentobarbital, phenobarbital, amobarbital, or thiopental.
飼主向け情報
メタドンは強力で厳格に管理されているオピオイド鎮痛薬です。注射で投与される場合、通常は動物病院内で獣医師の直接の監督下で行われます。
自宅での痛みの管理のために経口メタドンが処方された場合：
- 指示された用量を厳密に守ってください。 獣医師の相談なしに用量を増やしたり減らしたりしないでください。
-
非常に危険: この薬は、子供や他のペットの手の届かない安全な場所に保管してください。人間（特に子供）が誤って服用すると、致命的な呼吸抑制を引き起こす可能性があります。
- 軽い眠気、パンティング（あえぎ呼吸）、鳴き声、便秘などの副作用に注意してください。
- 直ちに獣医師の診察を受けてください: ペットが極度に無気力になったり、呼吸困難に陥ったり、呼吸が異常に遅くなった場合。
VetSheet医薬品リファレンスは獣医専門家の臨床意思決定支援を目的としており、専門的判断または製造業者の最新医薬品情報の代替にはなりません。