yingweiwo

Leucovorin Calcium

Alias: Folinic acid;Folinic acid calcium salt pentahydrate; Leucovorin calcium hydrate;Leucovorin Calcium; Calcium Folinate
Cat No.:V2027 Purity: ≥98%
Leucovorin calcium, a reduced folic acid andan active metabolite of folic acid, is a derivative of folic acid which can be used to increase levels of folic acid under conditions favoring folic acid inhibition.
Leucovorin Calcium
Leucovorin Calcium Chemical Structure CAS No.: 1492-18-8
Product category: DHFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
500mg
1g
2g
5g
10g
Other Sizes

Other Forms of Leucovorin Calcium:

  • Leucovorin (Folinic acid)
  • Leucovorin calcium hydrate
  • Folinic acid calcium hydrate
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Leucovorin calcium, a reduced folic acid and an active metabolite of folic acid, is a derivative of folic acid which can be used to increase levels of folic acid under conditions favoring folic acid inhibition. Leucovorin administration increases the level of reduced folates in tissues, which promotes the inhibition of thymidylate synthase in two murine colon tumors. Leucovorin, Gemcitabine, Oxaliplatin, and 5-fluorouracil is a powerful antitumor and immunomodulating regimen that can make the tumor cells a suitable means to induce an Ag-specific CTL response.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
The percentage of aberrant cells (Abs) and micronucleated binucleated cells (MNBN) increased concentration-dependently when MTX was used alone. The nuclear division index (NDI) falls as MTX concentration rises. Similarly, at every MTX concentration that was examined, the mitotic index (MI) likewise dropped. Leucovorin added at 50 μg/mL dramatically decreased the percentages of MNBN (40-68%) and Abs (36-77%). Additionally, at 5 μg/mL leucovorin, inhibitory effects were noted (12% to 54% for MNBN and 20% to 61% for Abs) [1].
ln Vivo
After receiving methotrexate (MTX) for three weeks, treatment with leucovorin (7.0 mg/kg; i.p.; every other day; for Balb/c juvenile male mice) appeared to counteract this growth suppression (MTX reduces bone growth in mice when administered chronically)[2].
Animal Protocol
Animal/Disease Models: 24 Balb/c young growing male mice aged 3 weeks (11.88 ± 0.25 g)[2]
Doses: 7.0 mg/kg
Route of Administration: intraperitoneal (ip)injection; every second day; for 3 weeks
Experimental Results: Following methotrexate (MTX) administration appears to reverse this growth inhibition.
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
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.
Duration of action: All routes: 3 to 6 hours.
Onset of action: Oral: 20 to 30 minutes. Intramuscular: 10 to 20 minutes. Intravenous: Less than 5 minutes.
Crosses blood-brain barrier in moderate amounts; largely concentrated in liver.
Elimination: Renal: 80-90%. Fecal: 5-8%.
For more Absorption, Distribution and Excretion (Complete) data for LEUCOVORIN (10 total), please visit the HSDB record page.
Metabolism / Metabolites
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.
In vivo, leucovorin calcium is rapidly and extensively converted to other tetrahydrofolic acid derivatives including 5-methyl tetrahydrofolate, which is the major transport and storage form of folate in the body. /Leucovorin calcium/
Hepatic and intestinal mucosal, mainly to 5-methyltetrahydrofolate (active). After oral administration, leucovorin is substantially (greater than 90%) and rapidly (within 30 minutes) metabolized. Metabolism is less extensive (about 66% after intravenous and 72% after intramuscular administration) and slower with parenteral administration.
Biological Half-Life
6.2 hours
Terminal half-life for total reduced folates: 6.2 hours.
Toxicity/Toxicokinetics
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Leucovorin (folinic acid; 5-formyltetrahydrofolic acid) and its levo- isomer, levoleucovorin, are folic acid derivatives that are normal components of breastmilk. Because leucovorin and levoleucovorin are used as therapeutic agents with potentially toxic drugs such as fluorouracil or methotrexate, the LactMed record of the drug it is used with should be consulted.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
~15%
Toxicity Data
Mouse(iv): LD50 732 mg/kg
Interactions
Concurrent use of leucovorin /with fluorouracil/ may increase the therapeutic and toxic effects of fluorouracil; although the two medications may be used together for therapeutic advantage, caution is necessary.
Exposure of tumor cells to reduced folates /like leucovorin/ before or with the fluoropyrimidines, 5-fluorouracil or 5-fluoro-2'deoxyuridine, results in a substantial increase in the activity of these drugs. Available evidence suggests that the mechanism of this synergism is a kinetic stabilization of complex formed between thymidylate synthase and fluorodeoxyuridylate that also involves a mole of the cofactor for the thymidylate synthase reaction, 5,10-methylenetetrahydrofolate. This effect results in an extended time of depletion of thymidine nucleotides with a resultant increased level of cell death.
Large dose of leucovorin may counteract the anticonvulsant effects of these medications: /barbiturate anticonvulsants, hydantoin anticonvulsants, primidone/.
The Sprague Dawley rat was used to demonstrate the effect of nitrous oxide, with and without folinic pretreatment, on reproductive indices and fetal development. ... Groups of animals were exposed to 70-75% nitrous oxide on day 9 of pregnancy with or without folinic acid 0.1 mg ip 12 hr before, and immediately before, exposure. Subsequent fetal development was compared with that of various control groups. There were no significant differences in fetal survival, but fetal wt were reduced in both groups exposed to nitrous oxide. Of the indices of skeletal maturity, the number of ossified sternebrae was reduced only in the nitrous oxide group not receiving folinic acid. The incidence of major skeletal abnormalities in the untreated nitrous oxide group was significantly increased to five times that of the control groups, whereas the incidence in the nitrous oxide group receiving folinic acid was not significantly different from control. It is concluded that pretreatment with folinic acid can at least partially reduce the teratogenic effects of nitrous oxide in the rat.
References

[1]. Inhibition of methotrexate-induced chromosomal damage by folinic acid in V79 cells. Mutat Res. 1998 Feb 2;397(2):221-8.

[2]. Effect of methotrexate and folinic acid on skeletal growth in mice. Acta Paediatr. 2003 Dec;92(12):1438-44.

Additional Infomation
Therapeutic Uses
Leucovorin is indicated for use in combination with agents such as fluorouracil or high-dose methotrexate, as second-line treatment of squamous cell head and neck carcinoma. /NOT included in US product labeling/
Antidotes
Leucovorin is indicated as a antidote to the toxic effects of folic acid antagonists such as methotrexate, pyrimethamine, or trimethoprim. Leucovorin also is indicated as a rescue after high-dose methotrexate therapy in osteosarcoma and as a part of chemotherapeutic treatment programs in the management of several forms of cancer. /Included in US product labeling/
Leucovorin is indicated to treat megaloblastic anemias associated with sprue, nutritional deficiency, pregnancy, and infancy when oral folic acid therapy is not feasible. Leucovorin is not recommended for use in the treatment of pernicious anemia or other megaloblastic anemias secondary to lack of vitamin B12, since it may produce a hematologic remission while neurologic manifestations continue to progress. /Included in US product labeling/
For more Therapeutic Uses (Complete) data for LEUCOVORIN (7 total), please visit the HSDB record page.
Drug Warnings
Since allergic reactions have been reported following oral and parenteral administration of folic acid, the possibility of allergic reactions to leucovorin should be considered.
There is a potential danger in administering leucovorin to patients with undiagnosed anemia, as leucovorin may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations of the disease while allowing neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of Vitamin Bl2 may prevent, halt, or improve neurologic changes caused by pernicious anemia.
When leucovorin rescue is used in conjunction with high dose methotrexate therapy, the drugs should be administered only by physicians experienced in cancer chemotherapy, in centers where facilities for measuring blood methotrexate concentrations are available. Leucovorin is usually effective in counteracting severe methotrexate toxicity in these regimens, but toxic reactions to methotrexate may occur despite leucovorin therapy, especially when the half-life of methotrexate is increased (eg, renal dysfunction). Therefore, it is extremely important that leucovorin be administered until the blood concentration of methotrexate declines to nontoxic concentrations.
Since leucovorin calcium enhances the toxicity of fluorouracil, adjunctive therapy with leucovorin calcium and fluorouracil should be given only by, or under the supervision of, physicians experienced in cancer chemotherapy and in the use of antimetabolites. /Leucovorin calcium/
For more Drug Warnings (Complete) data for LEUCOVORIN (10 total), please visit the HSDB record page.
Pharmacodynamics
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.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C21H25CAN7O7.5H2O
Molecular Weight
601.58
Exact Mass
511.112
CAS #
1492-18-8
Related CAS #
Folinic acid;58-05-9;Folinic acid calcium salt pentahydrate;6035-45-6;Folinic acid calcium hydrate;1097832-14-8
PubChem CID
135403648
Appearance
Off-white to light yellow solid powder
Melting Point
240-250ºC
LogP
1.411
Hydrogen Bond Donor Count
7
Hydrogen Bond Acceptor Count
10
Rotatable Bond Count
9
Heavy Atom Count
34
Complexity
911
Defined Atom Stereocenter Count
1
SMILES
C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
InChi Key
NPPBLUASYYNAIG-ZIGBGYJWSA-L
InChi Code
InChI=1S/C20H23N7O7.Ca.5H2O/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);;5*1H2/q;+2;;;;;/p-2/t12?,13-;;;;;;/m0....../s1
Chemical Name
L-Glutamic acid, N-(4-(((2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-, calcium salt (1:1), pentahydrate
Synonyms
Folinic acid;Folinic acid calcium salt pentahydrate; Leucovorin calcium hydrate;Leucovorin Calcium; Calcium Folinate
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO:<1 mg/mL
Water:40 mg/mL (66.5 mM)
Ethanol:<1 mg/mL
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6623 mL 8.3114 mL 16.6229 mL
5 mM 0.3325 mL 1.6623 mL 3.3246 mL
10 mM 0.1662 mL 0.8311 mL 1.6623 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Contact Us