QuickView for leucovorin (compound)

Summary
General Info

PubChem

PubChem Compound 135548

Name:	Leucovorin
PubChem Compound ID:	135548
Description:	The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.
Molecular formula:	C₂₀H₂₃N₇O₇
Molecular weight:	473.44 g/mol
Synonyms:	L-Glutamic acid, N-(4-((((6R)-2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-; Folinic acid; 5-FORMYL-5,6,7,8-TETRAHYDROFOLATE; FON; 73951-54-9; 6R-Leucovorin

DrugBank

Identification

Name:	Leucovorin
Name (isomeric):	DB00650
Drug Type:	small molecule
Description:	The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.
Synonyms:	Leucovorin calcium; Folinic acid; Calcium folinate; Leucovorin folinic acid; Folinic acid calcium salt USP27; Folinic acid calcium salt; L-leucovorin
Brand:	Leucal, Folinic acid-SF, Wellcovorin, Citrovorum factor, Calcium citrovorum factor
Category:	Vitamins/minerals, Vitamin B Complex, Antidote (to folic acid antagonists), Antineoplastic Adjuncts, Antianemic Agents
CAS number:	1492-18-8

Pharmacology

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.
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 Citrovoru... show more » 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. show less «
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 synth... show more » 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. show less «
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.
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
Toxicity:	LD₅₀>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Trimethoprim

The efficacy of Trimethoprim may be reduced by Leucovorin (folinic acid). The antibiotic, Trimethoprim, acts by blocking bacterial folic acid metabolism. Leucovorin may reduce the efficacy of Trimethoprim by providing an alternate source of folic acid. The therapeutic effect of Trimethoprim should be closely monitored.

Targets

Thymidylate synthase

Transporters

Multidrug resistance-associated protein 4

Canalicular multispecific organic anion transporter 1

Canalicular multispecific organic anion transporter 2