ホリナートカルシウム
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)**.
動物種別の用量
- Folate deficiency associated with pyrimethamine use · 5-15 mg (total dose) PO or parenterally once daily · PO/Parenteral · q24h
- Bone marrow suppression associated with pyrimethamine or trimethoprim/sulfa · 5 mg once daily · Not specified · q24h
- To prevent bone marrow toxicity associated with pyrimethamine · 1 mg/kg once daily · Not specified · q24h
- 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 · Most effective if given within 48 hours of overdose.
- 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 · A more practical approach would be to ensure that the horse receives green hay or pasture (high tetrahydrofolate levels in green roughage).
- Folate deficiency associated with pyrimethamine use · 5-15 mg (total dose) PO or parenterally once daily · PO/Parenteral · q24h
- 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 · Most effective if given within 48 hours of overdose. Dose is dependent on serum methotrexate concentration.
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
- 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)
薬物相互作用
- Barbiturates, Primidone, Phenytoin · Large doses of leucovorin may reduce the antiseizure efficacy of these agents.
- Fluorouracil (5-FU) · Leucovorin may increase both the antineoplastic efficacy and toxicity of 5-FU.
- Trimethoprim, Ormetoprim, Pyrimethamine · Leucovorin may reduce their efficacy somewhat; however, protozoa cannot utilize leucovorin, preserving the antimicrobial effect against them.
モニタリング
- Complete Blood Count (CBC)
- Methotrexate serum levels (if used for methotrexate overdoses; may require contacting a local human hospital)
過量投与
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.
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。