Folinic acid-SF - General Information
The active metabolite of folic acid. Folinic acid-SF is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [PubChem]
Pharmacology of Folinic acid-SF
Folinic acid-SF is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Folinic acid-SF is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Folinic acid-SF does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Folinic acid-SF has also been used to enhance the activity of fluorouracil.
Folinic acid-SF for patients
Folinic acid-SF Interactions
Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible pediatric patients.
Preliminary animal and human studies have shown that small quantities of systemically administered leucovorin enter the CSF primarily as 5-methyltetrahydro-folate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration. However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate.
Leucovorin may enhance the toxicity of 5-fluorouracil.
Folinic acid-SF Contraindications
Leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B12. A hematologic remission may occur while neurologic manifestations continue to progress.
Additional information about Folinic acid-SF
Folinic acid-SF Indication: For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Mechanism Of Action: As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Folinic acid-SF enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Leucovorin
Synonyms: Folinic acid; Folinic acid calcium salt; Folinic acid calcium salt USP27; L-leucovorin; Leucovorin calcium; Leucovorin folinic acid; Calcium folinate
Drug Category: Antidote (to folic acid antagonists); Antineoplastic Adjuncts; Vitamins/minerals; Antianemic Agents
Drug Type: Small Molecule; Approved
Absorption: Following oral administration, leucovorin is rapidly absorbed. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg.
Toxicity (Overdose): LD50>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
Protein Binding: ~15%
Biotransformation: Hepatic and intestinal mucosal, the main metabolite being the active 5-methyltetrahydrofolate. Leucovorin is readily converted to another reduced folate, 5,10-methylenetetrahydrofolate, which acts to stabilize the binding of fluorodeoxyridylic acid to thymidylate synthase and thereby enhances the inhibition of this enzyme.
Half Life: 6.2 hours
Dosage Forms of Folinic acid-SF: Solution Intravenous
Chemical IUPAC Name: (2R)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
Chemical Formula: C20H23N7O7
Leucovorin on Wikipedia: https://en.wikipedia.org/wiki/Leucovorin
Organisms Affected: Humans and other mammals