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Folinic acid
Folinic acid (INN) or leucovorin (USAN), generally administered as calcium folinate (or leucovorin calcium), is an adjuvant used in cancer chemotherapy involving the drug methotrexate. It is also used in synergistic combination with the chemotherapy agent 5-fluorouracil. Folinic acid is not folic acid. Additional recommended knowledge
Mechanism of actionFolinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g. tetrahydrofolate), and thus has vitamin activity which is equivalent to folic acid. However, since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate. Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presense of dihydrofolate reductase inhibition, so that some normal DNA replication and RNA transcription processes can proceed. Therapeutic useFolinic acid is administered at the appropriate time following methotrexate as part of a total chemotherapeutic plan, where it may "rescue" bone marrow and gastrointestinal mucosa cells from methotrexate. There is no apparent effect on preexisting methotrexate-induced nephrotoxicity.[1] While not specifically an antidote for methotrexate, folinic acid may also be useful in the treatment of acute methotrexate overdose. Different dosing protocols are used, but folinic acid should be re-dosed until the methotrexate level is less than 5 x 10-8 M (this can also be re-stated as < 0.05 μM) [2] Folinic acid is also used in combination with the chemotherapy agent 5-fluorouracil in treating colon cancer. In this case, folinic acid is not used for "rescue" purposes; rather, it enhances the effect of 5-fluorouracil on inhibiting thymidylate synthase. Folinic acid is also sometimes used to prevent toxic effects of high doses of antimicrobial dihydrofolate reductase inhibitors such as trimethoprim and pyrimethamine. Note on administrationFolinic acid should not be administered intrathecally. This may produce severe adverse effects or even death.[3] References
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Folinic_acid". A list of authors is available in Wikipedia. |