ホリナートカルシウム
Leucovorin Calcium
5-formyl tetrahydrofolic acid
別名: Citrovorum factor · 5-formyl tetrahydrofolate · citrovorin · folidan · FTHF · NSC-3590 · calcium folinate · calcifolin · calfonat · folinic acid calcium salt
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
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。
動物種別用量
🌎 NA — North America🌍 EU — Europe
犬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Folate deficiency associated with pyrimethamine use | 5-15 mg (total dose) PO or parenterally once daily | PO/Parenteral | q24h | — | 🌎 NA |
| Methotrexate overdose | 25-200 mg/m2 parenterally every 6 hours until methotrexate levels are less than 1 X 10 -8 M | Parenteral | q6h | Until methotrexate levels are < 1 X 10^-8 M | 🌎 NA |
- Methotrexate overdose: Most effective if given within 48 hours of overdose. Dose is dependent on serum methotrexate concentration.
猫
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Folate deficiency associated with pyrimethamine use | 5-15 mg (total dose) PO or parenterally once daily | PO/Parenteral | q24h | — | 🌎 NA |
| Bone marrow suppression associated with pyrimethamine or trimethoprim/sulfa | 5 mg once daily | Not specified | q24h | — | 🌎 NA |
| To prevent bone marrow toxicity associated with pyrimethamine | 1 mg/kg once daily | Not specified | q24h | — | 🌎 NA |
| Methotrexate overdose | 25-200 mg/m2 parenterally every 6 hours until methotrexate levels are less than 1 X 10 -8 M | Parenteral | q6h | Until methotrexate levels are < 1 X 10^-8 M | 🌎 NA |
- Methotrexate overdose: Most effective if given within 48 hours of overdose.
馬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Macrocytic anemia and neutropenia associated with pyrimethamine and/or trimethoprim (especially in pregnant mares) | 0.1-0.3 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
- Macrocytic anemia and neutropenia associated with pyrimethamine and/or trimethoprim (especially in pregnant mares): A more practical approach would be to ensure that the horse receives green hay or pasture (high tetrahydrofolate levels in green roughage).
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
ホリナートカルシウム（ロイコボリンカルシウム）は還元型葉酸誘導体であり、獣医療では主に救援薬または解毒剤として使用されます。
- 主な適応：ジヒドロ葉酸還元酵素阻害薬（ピリメタミン、トリメトプリム、オルメトプリムなど）に関連する血液毒性（骨髄抑制、大赤血球性貧血、好中球減少症など）の回復または予防に使用されます。
- メトトレキサート救援：人医療では高用量メトトレキサート化学療法の救援薬として日常的に使用されますが、獣医療ではメトトレキサートの偶発的な過剰投与の場合を除き、この目的で使用されることはまれです。
- 臨床的特徴：通常の葉酸とは異なり、生物学的活性を得るためにジヒドロ葉酸還元酵素による変換を必要としません。これにより、葉酸拮抗薬による酵素阻害を回避し、細胞機能に必要な葉酸を直接供給することができます。
作用機序
Leucovorin is a reduced form of folic acid that acts as a direct coenzyme in cellular metabolism.
- Bypassing DHFR: It does not require conversion by dihydrofolate reductase (DHFR) to become biologically active.
- Active Metabolite: It is converted in the body to active reduced forms, predominantly 5-methyltetrahydrofolate (5-methyl THF).
- DNA Synthesis: These reduced folates act as coenzymes in the synthesis of purine and pyrimidine nucleotides → essential for DNA synthesis and the maintenance of normal erythropoiesis (red blood cell production).
- Enzyme Inhibition: Leucovorin inhibits thymidylate synthase by stabilizing the binding of fluorodeoxyuridylic acid to the enzyme. This mechanism potentiates both the antineoplastic activity and the toxicity of fluorouracil (5-FU).
安全性・警告
禁忌
- Known intolerance or hypersensitivity to leucovorin
有害事象
- Gastrointestinal effects (noted in humans with oral administration)
- Seizures (very rare, noted in humans)
- Hypersensitivity reactions (very rare, noted in humans)
注意事項
Use with extreme caution in patients receiving systemic fluorouracil. Because of its calcium content, large intravenous doses should be given slowly and not bolused. In humans, folinic acid therapy may mask the signs associated with cobalamin (B-12) deficiency in megaloblastic anemias. When reconstituting powder with bacteriostatic water (which contains benzyl alcohol), avoid use in neonates or very small animals.
医薬品相互作用
Large doses of leucovorin may reduce the antiseizure efficacy of these agents.
Leucovorin may increase both the antineoplastic efficacy and toxicity of 5-FU.
Leucovorin may reduce their efficacy somewhat; however, protozoa cannot utilize leucovorin, preserving the antimicrobial effect against them.
監視
- Complete Blood Count (CBC)
- Methotrexate serum levels (if used for methotrexate overdoses; may require contacting a local human hospital)
薬物動態
半減期
吸収
In humans, oral bioavailability is dose-dependent (97% at 25 mg, decreasing to 37% at 100 mg). IM bioavailability is similar to IV. Peak levels of active reduced folates occur 1.7-2.4 hours after oral dosing, and about 10 minutes after IV administration.
分布
Apparent volume of distribution for both L- and D-forms is about 0.6 L/kg in dogs. About 50% of oral body stores of reduced folates are found in the liver.
代謝
Extensively metabolized to active reduced forms, predominantly 5-methyltetrahydrofolate (5-methyl THF).
消失
Excreted into the urine, primarily as 10-formyl-THF or 5,10-methyl-THF.
過剰投与
Except in situations where drug interactions are possible (e.g., with fluorouracil or antiseizure medications), an inadvertent overdose is unlikely to be of clinical concern.
製品
製剤
- Oral tablets
- Injection solution
- Powder for injection
ヒト用医薬品
- Leucovorin Calcium Oral Tablets: 5 mg, 15 mg, & 25 mg
- Leucovorin Calcium Injection Solution: 10 mg/mL in 5 mg single dose vials
- Leucovorin Calcium Powder for Injection: 50 mg, 100 mg, 200 mg & 350 mg in vials
規制ステータス
規制データなし: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Tablets and powder for injection should be stored below 40°C (preferably between 15-30°C) in a well-closed container and protected from light. Injection solution should be refrigerated between 2-8°C and protected from light. Reconstituted solutions made with sterile water should be used immediately; those made with bacteriostatic water are stable up to 7 days. IV solutions in LRS, Ringer's, or 0.9% NaCl are stable up to 24 hours at room temperature. Not compatible with fluorouracil solutions.
飼主向け情報
重要：メトトレキサート中毒の治療のためにこの薬を使用する場合、動物病院での入院管理下で獣医師の厳密な監督のもと投与される必要があります。
- 投与方法：経口投与の場合、食事の有無にかかわらず与えることができます。
- スケジュールの遵守：獣医師に指示された投与スケジュールを厳守することが非常に重要です。投与を忘れると、重篤な血液毒性の治療や予防に支障をきたす恐れがあります。
- 投与を忘れた場合：投与を忘れた場合は、獣医師に指示を仰いでください。専門家の指導なしに2回分を一度に与えないでください。
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。