Leucovorin Calcium

Leucovorin calcium (also known as folinic acid or citrovorum factor) is a reduced folic acid derivative primarily used in veterinary medicine as a **rescue agent** or **antidote**. * **Primary Indication**: It is used to reverse or prevent hematologic toxicity (such as bone marrow suppression, macrocytic anemia, and neutropenia) associated with dihydrofolate reductase inhibitors (e.g., pyrimethamine, trimethoprim, or ormetoprim). * **Methotrexate Rescue**: While routinely used in human medicine as a rescue agent for high-dose methotrexate chemotherapy, it is rarely used for this purpose in veterinary medicine, except in cases of accidental methotrexate overdose. * **Clinical Pearl**: Unlike standard folic acid, leucovorin does *not* require the enzyme dihydrofolate reductase to become biologically active. This allows it to bypass the enzymatic blockade caused by folic acid antagonists, directly supplying the necessary folates for cellular function.

กลไกการออกฤทธิ์: 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)**.

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