Indication: Used to treat osteosarcoma (after high dose methotrexate therapy), 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.
Pharmacology: Leucovorin 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. Leucovorin 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. Leucovorin 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. Leucovorin has also been used to enhance the activity of fluorouracil.
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). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.
Dosage Forms: LIQUID; POWDER FOR SOLUTION; SOLUTION; TABLET
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.
Interactions:
DrugBank: Interactions for Leucovorin
Interactions for Leucovorin:
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.
Chemical IUPAC Name: 2-[4-[(2-amino-5-formyl-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl)methylamino]benzoyl]aminopentanedioicacid
Chemical Formula: C20H23N7O7
Half Life: 6.2 hours
Drug Type: Approved Drug
# Accession No: APRD00698
CAS Registry Number: 1492-18-8
Leucovorin News (When available)
Plenary Session SnapshotDec 19, 2005 Medscape (subscription) ...radiotherapy alone (45 Gy in 25 fractions) or same RT with concurrent chemotherapy consisting of bolus 5-fluorouracil (5-FU) 350 mg/m 2 and folinic acid 20 mg ...
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