Leucovorin calciumProduct ingredient for Leucovorin

Name
Leucovorin calcium
Drug Entry
Leucovorin

Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin) is the 5-formyl derivative of tetrahydrofolic acid, a necessary co-factor in the body. Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009).

As folate analogs, leucovorin and levoleucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Injectable forms are also indicated for use in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible and for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects associated with methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.

Accession Number
DBSALT000342
Structure
Thumb
Synonyms
Anhydrous calcium folinate / Calcium folinate / Folic acid related compound A / Folinic acid (as calcium folinate)
UNII
RPR1R4C0P4
CAS Number
1492-18-8
Weight
Average: 511.508
Monoisotopic: 511.1128369
Chemical Formula
C20H21CaN7O7
InChI Key
KVUAALJSMIVURS-ZEDZUCNESA-L
InChI
InChI=1S/C20H23N7O7.Ca/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30;/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32);/q;+2/p-2/t12?,13-;/m0./s1
IUPAC Name
calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-hydroxy-5,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioate
SMILES
[Ca++].NC1=NC2=C(N(C=O)C(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)CN2)C(O)=N1
PubChem Compound
3624350
ChemSpider
14421
BindingDB
50247893
ChEBI
31340
ChEMBL
CHEMBL1201138
Wikipedia
Folinic_acid
Predicted Properties
PropertyValueSource
Water Solubility0.373 mg/mLALOGPS
logP1.11ALOGPS
logP-1.8ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.14ChemAxon
pKa (Strongest Basic)3.66ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area225.76 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity142.66 m3·mol-1ChemAxon
Polarizability45.51 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon