亞葉酸鈣
亞葉酸鈣（Leucovorin calcium，又稱甲醯四氫葉酸 folinic acid）是一種還原型的葉酸衍生物，在獸醫學中主要作為**救援劑**或**解毒劑**。 * **主要適應症**：用於逆轉或預防由二氫葉酸還原酶抑制劑（如乙胺嘧啶 pyrimethamine、甲氧苄啶 trimethoprim 或 奧美普林 ormetoprim）引起的血液毒性（如骨髓抑制、巨紅血球性貧血和嗜中性白血球低下）。 * **甲氨蝶呤救援**：雖然在人類醫學中常規用作高劑量甲氨蝶呤（methotrexate）化療的救援劑，但在獸醫學中極少用於此目的，除非發生意外的甲氨蝶呤中毒。 * **臨床要點**：與一般葉酸不同，亞葉酸鈣**不需要**經過二氫葉酸還原酶的轉換即可具有生物活性。這使其能夠繞過葉酸拮抗劑造成的酵素阻斷，直接提供細胞功能所需的葉酸。
作用機制: 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)**.
各物種劑量
- 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.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Known intolerance or hypersensitivity to leucovorin
不良反應
- Gastrointestinal effects (noted in humans with oral administration)
- Seizures (very rare, noted in humans)
- Hypersensitivity reactions (very rare, noted in humans)
藥物相互作用
- 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.
監測
- Complete Blood Count (CBC)
- Methotrexate serum levels (if used for methotrexate overdoses; may require contacting a local human hospital)
過量
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.
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