Identification

Name
Levomefolic acid
Accession Number
DB11256
Description

Levomefolic acid (INN) is the metabolite of folic acid (Vitamin B9) and it is a predominant active form of folate found in foods and in the blood circulation, accounting for 98% of folates in human plasma 8. It is transported across the membranes including the blood-brain barrier into various tissues where it plays an essential role in the DNA synthesis, cysteine cycle and regulation of homocysteine, where it methylates homocysteine and forms methionine and tetrahydrofolate (THF). Levomefolate is approved as a food additive and is designated a GRAS (generally regarded as safe) compound 13. It is available commercially as a crystalline form of the calcium salt (Metafolin(R)), which has the stability required for use as a supplement 8. Supplementation of levomefolic acid is desired over folic acid due to reduced potential for masking vitamin B12 deficiency symptoms.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 459.4558
Monoisotopic: 459.186631567
Chemical Formula
C20H25N7O6
Synonyms
  • (6S)-5-methyltetrahydrofolate
  • (6S)-5-Methyltetrahydrofolic acid
  • (6S)-5-MTHF
  • 5-methyl-(6S)-tetrahydrofolic acid
  • L-5-methyltetrahydrofolate
  • L-5-MTHF
  • L-methylfolate
  • Levomefolate
  • Levomefolic acid
  • LMSR
  • N-[4-[[[(6S)-2-Amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl]methyl]amino]benzoyl]-L-glutamic acid

Pharmacology

Indication

For the treatment and prevention of folate deficiency and for use as an antidote against folic acid antagonists. Contained in oral contraceptives to reduce the risk of neural tube defects arising from folic acid deficiency for pregnant women who conceived during use or shortly after the discontinuation of the product. Being studied for use as a treatment for cardiovascular diseases 7 and adjunct therapy for patients undergoing antidepressant pharmacotherapy 5,6.

Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine 6. Levomefolic acid is also involved in red blood cell formation 11.

Mechanism of action

Levomefolic acid plays a critical role in methylating homocysteines into methionine by acting as a methyl donor in a reaction catalyzed by vitamine B12-dependent methionine synthase. Homocysteine must either be further metabolized via transulfuration to become cysteine, taurine, and glutathione via a B6-dependent process, or re-methylated to become methionine again. Methionine formed from remethylation of homocysteine by levomefolic acid forms the downstream metabolite S-adenosylmethionine (SAMe), which is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters 10. Studies suggest that high plasma levels of homocysteine is associated with increased incidences of arterial plaque formation 9.

Absorption

Absorbed in the proximal small intestines via the active proton-coupled folate transporter (PCFT) that transports both oxidized and reduced folic acids. Passive diffusion also occurs at the proximal and distal portions of the small intestines 9. A single oral dose of 906nmol of levomefolic acid in healthy females resulted in the mean peak plasma concentration of 39.4nmol/L 8.

Volume of distribution

Circulates in its free form or loosely bound to plasma proteins

Protein binding

Approximately 56% bound to plasma proteins

Metabolism

Levomefolic acid is further converted into tetrahydrofolate (THF) via the vitamin B12-dependent enzyme methionine synthase before effective polyglutamylation by folylpolyglutamate synthetase (FPG). Polyglumate forms of folic acids are more effective substrates for associated enzymes in folate-dependent reactions.

Route of elimination

Mainly eliminated through renal or fecal excretion. Small proportion of excreted levomefolic acid is in unchanged form as over 99% of tissue folate is in polyglutamate form. Some portions of levomefolic acid is secreted into bile.

Half-life

The mean elimination half-life is approximately 3 hours after 5mg of oral L-methylfolate, administered daily for 7 days [775].

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Overdose of levomefolic acid is unlikely to cause clinically significant adverse events.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
CapecitabineThe risk or severity of adverse effects can be increased when Levomefolic acid is combined with Capecitabine.
CarbamazepineThe serum concentration of Carbamazepine can be decreased when it is combined with Levomefolic acid.
ColestipolThe serum concentration of Levomefolic acid can be decreased when it is combined with Colestipol.
FlucytosineThe risk or severity of adverse effects can be increased when Levomefolic acid is combined with Flucytosine.
FluorouracilThe risk or severity of adverse effects can be increased when Levomefolic acid is combined with Fluorouracil.
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Levomefolic acid.
GlucarpidaseThe serum concentration of the active metabolites of Levomefolic acid can be reduced when Levomefolic acid is used in combination with Glucarpidase resulting in a loss in efficacy.
MethylphenobarbitalThe serum concentration of the active metabolites of Methylphenobarbital can be reduced when Methylphenobarbital is used in combination with Levomefolic acid resulting in a loss in efficacy.
PhenobarbitalThe serum concentration of the active metabolites of Phenobarbital can be reduced when Phenobarbital is used in combination with Levomefolic acid resulting in a loss in efficacy.
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Levomefolic acid.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

Products

Product Ingredients
IngredientUNIICASInChI Key
Levomefolate calciumA9R10K3F2F151533-22-1VWBBRFHSPXRJQD-QNTKWALQSA-L
Levomefolate glucosamineQ65PL71Q1A1181972-37-1FZDRYCKUVGVDSO-KWWXADPNSA-N
Levomefolate magnesium1VZZ62R0811429498-11-2UNKHRTFYDNBUHK-QNTKWALQSA-L
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
L-Methylfolate CalciumTablet, coated7.5 mg/1OralVirtus Pharmaceuticals2015-02-09Not applicableUs
L-Methylfolate CalciumTablet, coated15 mg/1OralVirtus Pharmaceuticals2015-01-08Not applicableUs
L-Methylfolate CalciumTablet, coated7.5 mg/1OralVirtus Pharmaceuticals2012-03-152015-02-15Us
L-Methylfolate CalciumTablet7.5 mg/1OralSeton Pharmaceuticals2010-06-172012-10-18Us
L-Methylfolate CalciumTablet15 mg/1OralSeton Pharmaceuticals2010-06-302012-03-17Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BeyazLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitOralBayer HealthCare Pharmaceuticals Inc.2010-10-07Not applicableUs50419 40720180113 27003 xgvnkl
BeyazLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitOralBayer HealthCare Pharmaceuticals Inc.2010-10-07Not applicableUs50419 40720180113 27003 xgvnkl
Drospirenone, Ethinyl Estradiol and Levomefolate Calcium and Levomefolate CalciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 1/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)OralLupin Pharmaceuticals, Inc.2018-08-22Not applicableUs
Drospirenone, Ethinyl Estradiol and Levomefolate Calcium and Levomefolate CalciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 1/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)OralLupin Pharmaceuticals, Inc.2018-08-22Not applicableUs
Drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)OralSandoz Inc2015-08-01Not applicableUs
Drospirenone/Ethinyl Estradiol/Levomefolate Calcium and Levomefolate CalciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)OralSandoz Inc2016-10-12Not applicableUs
Drospirenone/Ethinyl Estradiol/Levomefolate Calcium and Levomefolate CalciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)OralSandoz Inc2016-10-12Not applicableUs
Drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calciumLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)OralSandoz Inc2015-08-01Not applicableUs
PramLyteLevomefolate magnesium (7 mg/1) + 1,2-docosahexanoyl-sn-glycero-3-phosphoserine calcium (6.4 mg/1) + 1,2-icosapentoyl-sn-glycero-3-phosphoserine calcium (800 ug/1) + Citric acid monohydrate (1.83 mg/1) + Cobamamide (50 ug/1) + Cocarboxylase (25 ug/1) + Escitalopram oxalate (10 mg/1) + Ferrous cysteine glycinate (13.6 mg/1) + Flavin adenine dinucleotide (25 ug/1) + Folic acid (1 mg/1) + Glycine betaine (500 ug/1) + Leucovorin (2.5 mg/1) + Magnesium ascorbate (24 mg/1) + NADH (25 ug/1) + Phosphatidyl serine (12 mg/1) + Pyridoxal phosphate (25 ug/1) + Sodium citrate (3.67 mg/1) + Zinc ascorbate (1 mg/1)KitOralAllegis Pharmaceuticals, LLC2015-09-112016-01-04Us
RajaniLevomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)OralActavis Pharma, Inc.2016-10-112018-10-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BumP DHALevomefolate magnesium (1 mg/1) + Cobamamide (500 mg/1) + Flavin adenine dinucleotide (1 mg/1) + Flavin mononucleotide (2 mg/1) + Iron (15 mg/1) + Leucovorin (1 mg/1) + Magnesium oxide (125 mg/1) + NADH (25 ug/1) + Omega-3 fatty acids (300 mg/1) + Potassium Iodide (250 ug/1) + Pyridoxal phosphate (5 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Zinc glycinate (15 1/1)CapsuleOralCenturion Labs2017-03-242017-04-17Us
ChromagenLevomefolic acid (750 ug/1) + Ascorbic acid (60 mg/1) + Cyanocobalamin (10 ug/1) + Ferrous asparto glycinate (25 mg/1) + Ferrous fumarate (50 mg/1) + Folic acid (250 ug/1) + Gastric intrinsic factor (100 mg/1) + Zinc (12 mg/1)CapsuleOralAvion Pharmaceuticals, Llc2017-01-10Not applicableUs
EnBrace HRLevomefolate magnesium (5.23 mg/1) + 1,2-docosahexanoyl-sn-glycero-3-phosphoserine calcium (6.4 mg/1) + 1,2-icosapentoyl-sn-glycero-3-phosphoserine calcium (800 ug/1) + Cobamamide (50 ug/1) + Cocarboxylase (25 ug/1) + Ferrous cysteine glycinate (13.6 mg/1) + Flavin adenine dinucleotide (25 ug/1) + Folic acid (1 mg/1) + Glycine betaine (500 ug/1) + Magnesium L-threonate (1 mg/1) + Leucovorin (2.5 mg/1) + Magnesium ascorbate (24 mg/1) + NADH (25 ug/1) + Phosphatidyl serine (12 mg/1) + Pyridoxal phosphate (25 ug/1) + Zinc ascorbate (1 mg/1)Capsule, delayed release pelletsOralJaymac Pharmaceuticals, Llc2011-08-12Not applicableUs
EnLyteLevomefolate magnesium (7 mg/1) + 1,2-docosahexanoyl-sn-glycero-3-phosphoserine calcium (6.4 mg/1) + 1,2-icosapentoyl-sn-glycero-3-phosphoserine calcium (800 ug/1) + Citric acid monohydrate (1.83 mg/1) + Cobamamide (50 ug/1) + Cocarboxylase (25 ug/1) + Ferrous cysteine glycinate (13.6 mg/1) + Flavin adenine dinucleotide (25 ug/1) + Folic acid (1 mg/1) + Glycine betaine (500 ug/1) + Magnesium L-threonate (1 mg/1) + Leucovorin (2.5 mg/1) + Magnesium ascorbate (24 mg/1) + NADH (25 ug/1) + Phosphatidyl serine (12 mg/1) + Pyridoxal phosphate (25 ug/1) + Sodium citrate (3.67 mg/1) + Zinc ascorbate (1 mg/1)Capsule, delayed release pelletsOralJaymac Pharmaceuticals Llc2011-08-12Not applicableUs
FlorivaLevomefolate glucosamine (162 ug/1) + Ascorbic acid (75 mg/1) + Beta carotene (1000 [iU]/1) + Biotin (40 ug/1) + Cholecalciferol (600 [iU]/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (6 ug/1) + Folic acid (100 ug/1) + Nicotinamide (15 mg/1) + Pyridoxine (1.8 mg/1) + Riboflavin (1.5 mg/1) + Sodium fluoride (0.5 mg/1) + Thiamine chloride (1.3 mg/1) + Vitamin A acetate (1000 [iU]/1) + Vitamin E (20 [iU]/1) + Zinc gluconate (5 mg/1)Tablet, chewableOralBonGeo Pharmaceuticals, Inc.2014-10-15Not applicableUs
FlorivaLevomefolate glucosamine (162 ug/1) + Ascorbic acid (75 mg/1) + Beta carotene (1000 [iU]/1) + Biotin (40 ug/1) + Cholecalciferol (600 [iU]/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (6 ug/1) + Folic acid (100 ug/1) + Nicotinamide (15 mg/1) + Pyridoxine (1.8 mg/1) + Riboflavin (1.5 mg/1) + Sodium fluoride (1 mg/1) + Thiamine chloride (1.3 mg/1) + Vitamin A acetate (1000 [iU]/1) + Vitamin E (20 [iU]/1) + Zinc gluconate (5 mg/1)Tablet, chewableOralBonGeo Pharmaceuticals, Inc.2014-10-15Not applicableUs
FlorivaLevomefolate glucosamine (162 ug/1) + Ascorbic acid (75 mg/1) + Beta carotene (1000 [iU]/1) + Biotin (40 ug/1) + Cholecalciferol (600 [iU]/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (6 ug/1) + Folic acid (100 ug/1) + Nicotinamide (15 mg/1) + Pyridoxine (1.8 mg/1) + Riboflavin (1.5 mg/1) + Sodium fluoride (0.25 mg/1) + Thiamine chloride (1.3 mg/1) + Vitamin A acetate (1000 [iU]/1) + Vitamin E (20 [iU]/1) + Zinc gluconate (5 mg/1)Tablet, chewableOralBonGeo Pharmaceuticals, Inc.2015-09-10Not applicableUs
Floriva PlusLevomefolate glucosamine (29.7 ug/1mL) + Ascorbic acid (32 mg/1mL) + Biotin (3 ug/1mL) + Cholecalciferol (400 [iU]/1mL) + Cyanocobalamin (2 ug/1mL) + Riboflavin 5'-phosphate sodium (0.6 mg/1mL) + Nicotinamide (2 mg/1mL) + Pantothenic acid (1 mg/1mL) + Pyridoxine hydrochloride (0.4 mg/1mL) + Sodium fluoride (0.25 mg/1mL) + Thiamine hydrochloride (0.5 mg/1mL) + Vitamin A acetate (1150 [iU]/1mL) + Vitamin E (5 [iU]/1mL)Solution / dropsOralBonGeo Pharmaceuticals, Inc.2016-06-202020-01-21Us
FoleneLevomefolic acid (2 mg/1) + Acetylcysteine magnesium (100 mg/1) + Calcium citrate tetrahydrate (200 mg/1) + Cholecalciferol (3775 [iU]/1)CapsuleOralGm Pharmaceuticals2016-08-102017-01-31Us
L-Methyl MCLevomefolate calcium (6 mg/1) + Cyanocobalamin (1 mg/1) + Pyridoxine (50 mg/1) + Riboflavin (5 mg/1)Tablet, coatedOralVirtus Pharmaceuticals2012-03-012015-02-23Us

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pteridines and derivatives
Sub Class
Pterins and derivatives
Direct Parent
Tetrahydrofolic acids
Alternative Parents
Glutamic acid and derivatives / N-acyl-alpha amino acids / Hippuric acids / Aminobenzamides / Aniline and substituted anilines / Phenylalkylamines / Benzoyl derivatives / Dialkylarylamines / Aminopyrimidines and derivatives / Secondary alkylarylamines
show 13 more
Substituents
Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aminobenzamide / Aminobenzoic acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle
show 35 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tetrahydrofolic acid (CHEBI:15641)

Chemical Identifiers

UNII
8S95DH25XC
CAS number
31690-09-2
InChI Key
ZNOVTXRBGFNYRX-STQMWFEESA-N
InChI
InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1
IUPAC Name
(2S)-2-{[4-({[(6S)-2-amino-5-methyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
SMILES
CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)N=C(N)N2

References

General References
  1. Fruzzetti F: Beyaz(R): an oral contraceptive fortified with folate. Womens Health (Lond). 2012 Jan;8(1):13-9. doi: 10.2217/whe.11.68. [PubMed:22171769]
  2. Bart S Sr, Marr J, Diefenbach K, Trummer D, Sampson-Landers C: Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study. Contraception. 2012 Jan;85(1):42-50. doi: 10.1016/j.contraception.2011.05.013. Epub 2011 Jul 13. [PubMed:22067790]
  3. Rapkin RB, Creinin MD: The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium. Expert Opin Pharmacother. 2011 Oct;12(15):2403-10. doi: 10.1517/14656566.2011.610791. Epub 2011 Aug 31. [PubMed:21877996]
  4. Wilson SM, Bivins BN, Russell KA, Bailey LB: Oral contraceptive use: impact on folate, vitamin B(6), and vitamin B(1)(2) status. Nutr Rev. 2011 Oct;69(10):572-83. doi: 10.1111/j.1753-4887.2011.00419.x. [PubMed:21967158]
  5. Ginsberg LD, Oubre AY, Daoud YA: L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci. 2011 Jan;8(1):19-28. [PubMed:21311704]
  6. Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV: Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial. Prim Care Companion CNS Disord. 2013;15(4). pii: PCC.13m01520. doi: 10.4088/PCC.13m01520. Epub 2013 Aug 29. [PubMed:24392264]
  7. Willems FF, Boers GH, Blom HJ, Aengevaeren WR, Verheugt FW: Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol. 2004 Mar;141(5):825-30. Epub 2004 Feb 9. [PubMed:14769778]
  8. Pietrzik K, Bailey L, Shane B: Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. [PubMed:20608755]
  9. Miraglia N, Agostinetto M, Bianchi D, Valoti E: Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats. Minerva Ginecol. 2016 Apr;68(2):99-105. [PubMed:27008238]
  10. Miller AL: The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26. [PubMed:18950248]
  11. Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K: Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006 Jul;84(1):156-61. [PubMed:16825690]
  12. Dailymed [Link]
  13. FDA Center for Drug Evaluation and Research: Summary Review [Link]
  14. Cayman Chemicals Safety Data Sheet [Link]
  15. Dailymed L-Methyl-MC-NAC Tablets [Link]
KEGG Compound
C00440
PubChem Compound
444412
PubChem Substance
347827954
ChemSpider
392351
BindingDB
50391007
RxNav
1025342
ChEBI
15641
ChEMBL
CHEMBL1231574
ZINC
ZINC000002005305
PharmGKB
PA166129561
PDBe Ligand
THH
Drugs.com
Drugs.com Drug Page
Wikipedia
Levomefolic_acid
PDB Entries
1b02 / 1q8j / 1tls / 1tsn / 1u1j / 1wsv / 1xpg / 1xr2 / 1zp4 / 2e7f
show 23 more
MSDS
Download (51 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentPolycystic Ovaries Syndrome1
4TerminatedTreatmentAnemia1
4WithdrawnTreatmentMenstrual Related Mood Disorder / Premenstrual Dysphoric Disorder / Premenstrual Syndrome / Premenstrual tension with edema1
3CompletedPreventionContraception1
3WithdrawnTreatmentContraception1
2, 3CompletedTreatmentAttention Deficit Hyperactivity Disorder (ADHD) / Attention Deficit/Hyperactivity Disorder1
1CompletedNot AvailableContraception / Oral Contraception / Ovulation Inhibition / Pharmacology, Clinical1
1CompletedTreatmentContraception2
1CompletedTreatmentContraception / Ovulation Inhibition1
1, 2RecruitingTreatmentPostpartum Anemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Capsule, delayed release pelletsOral
Solution / dropsOral
TabletOral
TabletOral15 mg/1
TabletOral7.5 mg/1
Tablet, coatedOral15 mg/1
Tablet, coatedOral7.5 mg/1
Tablet, coatedOral
CapsuleOral
Suspension / dropsOral
KitOral
Tablet, film coatedOral
Capsule, gelatin coatedOral
LiquidOral
Tablet, chewableOral
PowderOral; Topical
PowderOral
Capsule, liquid filledOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7163931No2007-01-162021-12-20Us
US6958326No2005-10-252021-12-20Us
US5798338No1998-08-252015-07-10Us
US6441168No2002-08-272022-07-30Us
US8617597No2013-12-312030-02-08Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)221MSDS
water solubilityApproximately 0.3 mg/mlCayman Chemical Safety Data Sheet
Predicted Properties
PropertyValueSource
Water Solubility0.332 mg/mLALOGPS
logP-0.58ALOGPS
logP-3.8ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.5ChemAxon
pKa (Strongest Basic)3.54ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area198.48 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.68 m3·mol-1ChemAxon
Polarizability46.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-0312900000-1e7ffc57c6bfdc0e8fe9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-0924300000-c9fa222e5e77153ca411
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-1921000000-012fee21d119d325c696
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0001900000-dd3b789dceaf2f1cb9a7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0904-1245900000-aa2092d5d8304fe7f772
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-7951200000-24cf3f653b8a2e0b9b29

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Cofactor
General Function
Zinc ion binding
Specific Function
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofola...
Gene Name
MTR
Uniprot ID
Q99707
Uniprot Name
Methionine synthase
Molecular Weight
140525.91 Da
References
  1. Pietrzik K, Bailey L, Shane B: Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. [PubMed:20608755]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Methotrexate transporter activity
Specific Function
Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithel...
Gene Name
SLC46A1
Uniprot ID
Q96NT5
Uniprot Name
Proton-coupled folate transporter
Molecular Weight
49770.04 Da
References
  1. Zhao R, Aluri S, Goldman ID: The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. Mol Aspects Med. 2017 Feb;53:57-72. doi: 10.1016/j.mam.2016.09.002. Epub 2016 Sep 21. [PubMed:27664775]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Reduced folate carrier activity
Specific Function
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely th...
Gene Name
SLC19A1
Uniprot ID
P41440
Uniprot Name
Folate transporter 1
Molecular Weight
64867.62 Da
References
  1. Hou Z, Matherly LH: Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 2014;73:175-204. doi: 10.1016/B978-0-12-800223-0.00004-9. [PubMed:24745983]

Drug created on December 03, 2015 09:51 / Updated on June 12, 2020 10:53

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates