Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C20H23N7O6.2Na |
| Molecular Weight | 503.4195 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)CNC3=C1C(O)=NC(N)=N3
InChI
InChIKey=KKIWVYLOTHCGRV-NJHZPMQHSA-L
InChI=1S/C20H25N7O6.2Na/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);;/q;2*+1/p-2/t12-,13-;;/m0../s1
For people with MTHFR gene variations, supplementing with the already activated form of folate (5-MTHF/5- METHYLTETRAHYDROFOLATE/LEVOMEFOLIC ACID) is far more effective in providing this form of folate than introducing the pre-converted form to the body through typical folate supplements. L-Methylfolate (5-MTHF) supplements provide the active form of folate naturally present in the body and available for biological action. 5-MTHF—the “active” form of folate that is able to pass the blood brain barrier. However, without a properly functioning methylenetetrahydrofolate reductase, MTHFR this conversion cannot take place and folate is not converted to forms that can cross the blood brain barrier. That is where 5-MTHF supplements come in. Levomefolate calcium is structurally identical to L-5-methyltetrahydrofolate (L-5-methyl-THF), a metabolite of vitamin B9. Mean baseline concentrations of about 15 nmol/L are reached in populations without folate food fortification under normal nutritional conditions. Orally administered levomefolate calcium is absorbed and is incorporated into the body folate pool. Peak plasma concentrations of about 50 nmol/L above baseline are reached within 0.5 – 1.5 hours after single oral administration of 0.451 mg levomefolate calcium. Steady state conditions for total folate in plasma after intake of 0.451 mg levomefolate calcium. In red blood cells, achievement of steady state is delayed due to the long lifespan of red blood cells of about 120 days. Levomefolate calcium is a part of contraceptive tablets: SAFYRA. Safyral is an estrogen/progestin COC (Combined Oral Contraceptive) containing a folate, indicated for use by women to: prevent pregnancy and raise folate levels in women who choose to use an oral contraceptive for contraception. COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.
CNS Activity
Approval Year
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | SAFYRAL Approved Use1.1 Oral Contraceptive: Safyral is indicated for use by women to prevent pregnancy. 1.2 Folate Supplementation
Safyral is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product. Launch Date2010 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
57.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22909145/ |
0.451 mg single, oral dose: 0.451 mg route of administration: Oral experiment type: SINGLE co-administered: ETHINYL ESTRADIOL |
L-5-METHYLTETRAHYDROFOLATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
370 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22909145/ |
0.451 mg single, oral dose: 0.451 mg route of administration: Oral experiment type: SINGLE co-administered: ETHINYL ESTRADIOL |
L-5-METHYLTETRAHYDROFOLATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22909145/ |
0.451 mg single, oral dose: 0.451 mg route of administration: Oral experiment type: SINGLE co-administered: ETHINYL ESTRADIOL |
L-5-METHYLTETRAHYDROFOLATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
44% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22909145/ |
0.451 mg single, oral dose: 0.451 mg route of administration: Oral experiment type: SINGLE co-administered: ETHINYL ESTRADIOL |
L-5-METHYLTETRAHYDROFOLATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency. | 2004-09-15 |
|
| Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells. | 2004-09 |
|
| Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction. | 2004-07 |
|
| Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity. | 2004-06 |
|
| Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol. | 2004-05-21 |
|
| The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma. | 2004-05-17 |
|
| Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation. | 2004-05-10 |
|
| A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. | 2004-04-29 |
|
| Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate. | 2004-04 |
|
| The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men. | 2004-04 |
|
| Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier. | 2004-04 |
|
| 5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism. | 2004-03-15 |
|
| Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. | 2004-03 |
|
| Folic acid rescues nitric oxide-induced neural tube closure defects. | 2004-03 |
|
| Sodium-dependent methotrexate carrier-1 is expressed in rat kidney: cloning and functional characterization. | 2004-03 |
|
| Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications. | 2004-02-17 |
|
| Comparative study on pressure and temperature stability of 5-methyltetrahydrofolic acid in model systems and in food products. | 2004-02-11 |
|
| Solid-phase extraction-electrospray ionization mass spectrometry for the quantification of folate in human plasma or serum. | 2004-02-01 |
|
| Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients. | 2004-02 |
|
| Folate, homocysteine, endothelial function and cardiovascular disease. | 2004-02 |
|
| Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. | 2004-02 |
|
| Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms: relationships with 5-fluorouracil sensitivity. | 2004-01-26 |
|
| Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke. | 2004-01 |
|
| Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore. | 2003-12-18 |
|
| Cobalamin-dependent methionine synthase: probing the role of the axial base in catalysis of methyl transfer between methyltetrahydrofolate and exogenous cob(I)alamin or cob(I)inamide. | 2003-12-16 |
|
| Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism. | 2003-12 |
|
| Thrombophilia and pregnancy. | 2003-11-14 |
|
| Age dependence of the influence of methylenetetrahydrofolate reductase genotype on plasma homocysteine level. | 2003-11-01 |
|
| Folate improves endothelial function in patients with coronary heart disease. | 2003-11 |
|
| Hyperhomocystinemia in children with inflammatory bowel disease. | 2003-11 |
|
| Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae. | 2003-10-31 |
|
| Characterization of a pseudogene for murine methylenetetrahydrofolate reductase. | 2003-10 |
|
| Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype. | 2003-09-09 |
|
| Reduced folate transport to the CNS in female Rett patients. | 2003-08-26 |
|
| Uptake of 5-methyltetrahydrofolate into PC-3 human prostate cancer cells is carrier-mediated. | 2003-08 |
|
| Antisense modulation of the coding or regulatory sequence of the folate receptor (folate binding protein-1) in mouse embryos leads to neural tube defects. | 2003-07 |
|
| Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility. | 2003-06-27 |
|
| A mass spectrometric validated high-performance liquid chromatography procedure for the determination of folates in foods. | 2003-06-18 |
|
| Analysis of the human folate receptor beta gene for an association with neural tube defects. | 2003-06 |
|
| Model studies on the stability of folic acid and 5-methyltetrahydrofolic acid degradation during thermal treatment in combination with high hydrostatic pressure. | 2003-05-21 |
|
| Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. | 2003-05 |
|
| Specific and sensitive quantification of folate vitamers in foods by stable isotope dilution assays using high-performance liquid chromatography-tandem mass spectrometry. | 2003-05 |
|
| Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation. | 2003-05 |
|
| Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate? | 2003-04-01 |
|
| Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry. | 2003-02-26 |
|
| Transport of 5-formyltetrahydrofolate into primary cultured cerebellar granule cells. | 2003-02-07 |
|
| Affinity extraction combined with stable isotope dilution LC/MS for the determination of 5-methyltetrahydrofolate in human plasma. | 2003-02-01 |
|
| Transport of 5-formyltetrahydrofolate into primary cultured rat astrocytes. | 2003-02-01 |
|
| Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. | 2003-02 |
|
| Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution. | 2002-12 |
Patents
| Name | Type | Language | ||
|---|---|---|---|---|
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Common Name | English | ||
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Preferred Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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1423663-76-6
Created by
admin on Mon Mar 31 23:05:03 GMT 2025 , Edited by admin on Mon Mar 31 23:05:03 GMT 2025
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PRIMARY | |||
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135565435
Created by
admin on Mon Mar 31 23:05:03 GMT 2025 , Edited by admin on Mon Mar 31 23:05:03 GMT 2025
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PRIMARY | |||
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B3KYL5163W
Created by
admin on Mon Mar 31 23:05:03 GMT 2025 , Edited by admin on Mon Mar 31 23:05:03 GMT 2025
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PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD
