Leucovorin

Identification

Summary

Leucovorin is a folate analog used to treat the toxic effects of methotrexate and other folate antagonists, to treat megaloblastic anemia, and to provide palliative treatment of colorectal cancer.

Brand Names
EnBrace HR, EnLyte, Lederle Leucovorin
Generic Name
Leucovorin
DrugBank Accession Number
DB00650
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 473.446
Monoisotopic: 473.165896109
Chemical Formula
C20H23N7O7
Synonyms
  • (5-formyl-5,6,7,8-tetrahydropteroyl)glutamate
  • 10-Formyl-7,8-dihydrofolic acid
  • 5-Formyl-5,6,7,8-tetrahydrofolic acid
  • 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic acid
  • 5-Formyltetrahydrofolate
  • 5-formyltetrahydrofolic acid
  • Acide folinique
  • Acido folinico
  • Folinate
  • Folinic acid
  • L(-)-5-Formyl-5,6,7,8-tetrahydrofolic acid
  • Leucovorinum
  • N-(5-formyl-5,6,7,8-tetrahydropteroyl)-L-glutamic acid
  • N5-Formyl-5,6,7,8-tetrahydrofolic acid
  • N5-Formyltetrahydrofolic acid

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
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

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 synthetase.

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.

Volume of distribution

Not Available

Protein binding

~15%

Metabolism

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.

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Route of elimination

Not Available

Half-life

6.2 hours

Clearance

Not Available

Adverse Effects
Medicalerrors
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Toxicity

LD50>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.

Pathways
PathwayCategory
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)Disease
Folate MetabolismMetabolic
Methotrexate Action PathwayDrug action
Folate Malabsorption, HereditaryDisease
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
AcamprosateThe excretion of Acamprosate can be decreased when combined with Leucovorin.
Acetylsalicylic acidThe excretion of Leucovorin can be decreased when combined with Acetylsalicylic acid.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Leucovorin.
AllopurinolThe excretion of Allopurinol can be decreased when combined with Leucovorin.
AlprostadilThe excretion of Alprostadil can be decreased when combined with Leucovorin.
Aminohippuric acidThe excretion of Leucovorin can be decreased when combined with Aminohippuric acid.
ApalutamideThe excretion of Leucovorin can be decreased when combined with Apalutamide.
AtalurenThe excretion of Leucovorin can be decreased when combined with Ataluren.
AvatrombopagThe excretion of Leucovorin can be decreased when combined with Avatrombopag.
AvibactamThe excretion of Avibactam can be decreased when combined with Leucovorin.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Leucovorin calciumRPR1R4C0P41492-18-8KVUAALJSMIVURS-ZEDZUCNESA-L
Leucovorin calcium pentahydrateR3W57OBQ5W6035-45-6NPPBLUASYYNAIG-ZIGBGYJWSA-L
Leucovorin sodium4MXU9LJS4Q163254-40-8FSDMNNPYPVJNAT-RIWFDJIXSA-L
Product Images
International/Other Brands
Uzel / Wellcovorin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Calcium FolinateInjection, solution10 mg/1mLIntramuscular; IntravenousTeva Parenteral Medicines, Inc2011-07-122014-07-31US flag
Calcium FolinateInjection, solution10 mg/1mLIntramuscular; IntravenousTeva Parenteral Medicines, Inc2011-07-122014-02-28US flag
Lederle LeucovorinTablet5 mgOralPfizer Canada Ulc1996-10-25Not applicableCanada flag
Lederle Leucovorin - Liq Im IV 10mg/mlLiquid10 mg / mLIntramuscular; IntravenousWyeth Ayerst Canada Inc.1997-02-042001-10-29Canada flag
Lederle Leucovorin 350mg/vialPowder, for solution350 mg / vialIntramuscular; IntravenousLederle Cyanamid Canada Inc.1991-12-311999-04-12Canada flag
Lederle Leucovorin 50mg/vialPowder, for solution50 mg / vialIntramuscular; IntravenousLederle Cyanamid Canada Inc.1991-12-311997-08-14Canada flag
Lederle Leucovorin Liq 10mg/mlLiquid10 mg / mLIntramuscular; IntravenousLederle Cyanamid Canada Inc.1991-12-311999-04-12Canada flag
Lederle Leucovorin-pws Im IV 350mg/vialPowder, for solution350 mg / vialIntramuscular; IntravenousWyeth Ayerst Canada Inc.1997-02-042002-05-17Canada flag
Lederle Leucovorin-pws Im IV 50mg/vialPowder, for solution50 mg / vialIntramuscular; IntravenousWyeth Ayerst Canada Inc.1997-02-042001-06-05Canada flag
Leucovorin Ca Inj (pharm. Bulk Vial) 10mg/mlLiquid10 mg / mLIntravenousDavid Bull Laboratories (Pty) Ltd.1992-12-311997-08-14Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LeucovorinInjection, powder, for solution20 mg/1mLIntramuscular; IntravenousBlue Point Laboratories2016-07-01Not applicableUS flag
LeucovorinInjection, powder, for solution10 mg/1mLIntramuscular; IntravenousBlue Point Laboratories2016-07-01Not applicableUS flag
Leucovorin CalciumInjection, powder, lyophilized, for solution500 mg/50mLIntramuscular; IntravenousFresenius Kabi USA, LLC2010-09-18Not applicableUS flag
Leucovorin CalciumTablet5 mg/1OralRemedy Repack2013-03-122014-03-12US flag
Leucovorin CalciumTablet25 mg/1OralMylan Institutional Inc.1997-08-27Not applicableUS flag
Leucovorin CalciumInjection, powder, lyophilized, for solution350 mg/17.5mLIntramuscular; IntravenousSagent Pharmaceuticals2012-09-15Not applicableUS flag
Leucovorin CalciumInjection, powder, lyophilized, for solution350 mg/17.5mLIntramuscular; IntravenousBedford Pharmaceuticals2001-09-282013-05-31US flag
Leucovorin CalciumTablet25 mg/1OralLeading Pharma, Llc2020-11-16Not applicableUS flag
Leucovorin CalciumTablet25 mg/1OralMajor Pharmaceuticals1993-02-22Not applicableUS flag
Leucovorin CalciumTablet5 mg/1OralRemedy Repack2012-07-182013-07-19US flag00555 0484 01 nlmimage10 092b84cc
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Folina Tablets 15mgTabletOralPHARM-D SDN. BHD.2020-09-08Not applicableMalaysia flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
FERPLEX FOL 40 MG + 0.185 MG/15 ML ORAL ÇÖZELTİ, 10 ADETLeucovorin calcium pentahydrate (0.185 mg) + Iron protein succinylate (40 mg)SolutionOralABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
KOMFER FOL 40 MG/185 MCG ORAL COZELTI, 10 FLK.Leucovorin calcium pentahydrate (0.235 mg) + Iron protein succinylate (800 mg)SolutionOralKOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş.2020-08-14Not applicableTurkey flag
KOMFER FOL 40 MG/185 MCG ORAL COZELTI, 20 FLK.Leucovorin calcium pentahydrate (0.235 mg) + Iron protein succinylate (800 mg)SolutionOralKOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş.2020-08-14Not applicableTurkey flag
PramLyteLeucovorin (2.5 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) + Betaine (500 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) + Levomefolate magnesium (7 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 flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BumP DHALeucovorin (1 mg/1) + Cobamamide (500 mg/1) + Flavin adenine dinucleotide (1 mg/1) + Flavin mononucleotide (2 mg/1) + Iron (15 mg/1) + Levomefolate magnesium (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 flag
Calcium FolinateLeucovorin calcium (10 mg/1mL)Injection, solutionIntramuscular; IntravenousTeva Parenteral Medicines, Inc2011-07-122014-07-31US flag
Calcium FolinateLeucovorin calcium (10 mg/1mL)Injection, solutionIntramuscular; IntravenousTeva Parenteral Medicines, Inc2011-07-122014-02-28US flag
CALCIUM FOLINATE DBL 100 MG/10 ML ENJEKTABL SOLUSYONLeucovorin (100 mg/10ml)SolutionIntramuscular; IntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
CALCIUM FOLINATE DBL 300 MG/30 ML FLAKON ENJEKTABL SOL.Leucovorin (300 mg/30ml)SolutionIntramuscular; IntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
CALCIUM FOLINATE DBL 5 ML 50 MG FLAKON, 1 ADETLeucovorin (50 mg/5ml)SolutionIntramuscular; IntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
CALCIUM FOLINATE DBL 7,5 MG/ML ENJ. SOLUSYON 1 AMPULLeucovorin calcium (7.5 mg/ml)SolutionIntramuscular; IntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
DyzbacLeucovorin (1 mg/1) + Ascorbic acid (125 mg/1) + Cholecalciferol (500 [iU]/1) + Lipoic acid (150 mg/1) + Mecobalamin (1 mg/1) + Pyridoxal phosphate (12.5 mg/1) + Resveratrol (50 mg/1) + Ubidecarenone (25 mg/1)TabletOralBasiem2015-11-052016-01-01US flag
DyzbacLeucovorin (1 mg/1) + Ascorbic acid (150 mg/1) + Cholecalciferol (0.0125 mg/1) + Lipoic acid (125 mg/1) + Mecobalamin (1 mg/1) + Pyridoxal phosphate (12.5 mg/1) + Resveratrol (50 mg/1) + Ubidecarenone (50 mg/1)TabletOralBasiem2015-10-282015-11-01US flag
EnBrace HRLeucovorin (2.5 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) + Betaine (500 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) + Magnesium L-threonate (1 mg/1) + Levomefolate magnesium (5.23 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 flag

Categories

ATC Codes
V03AF06 — Sodium folinateV03AF03 — Calcium folinate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Glutamic acid and derivatives
Alternative Parents
N-acyl-alpha amino acids / Hippuric acids / Pterins and derivatives / Aminobenzamides / Phenylalkylamines / Aniline and substituted anilines / Benzoyl derivatives / Secondary alkylarylamines / Hydroxypyrimidines / Dicarboxylic acids and derivatives
show 10 more
Substituents
Amine / Amino acid / Aminobenzamide / Aminobenzoic acid or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
formyltetrahydrofolic acid (CHEBI:15640)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Q573I9DVLP
CAS number
58-05-9
InChI Key
VVIAGPKUTFNRDU-ABLWVSNPSA-N
InChI
InChI=1S/C20H23N7O7/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)/t12?,13-/m0/s1
IUPAC Name
(2S)-2-[(4-{[(2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
SMILES
[H]C(=O)N1C(CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2

References

Synthesis Reference

James C. Wisowaty, Roy A. Swaringen, David A. Yeowell, "Synthesis of leucovorin." U.S. Patent US4500711, issued July, 1955.

US4500711
General References
  1. Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. [Article]
  2. Zittoun J: Pharmacokinetics and in vitro studies of l-leucovorin. Comparison with the d and d,l-leucovorin. Ann Oncol. 1993;4 Suppl 2:1-5. [Article]
  3. Chuang VT, Suno M: Levoleucovorin as replacement for leucovorin in cancer treatment. Ann Pharmacother. 2012 Oct;46(10):1349-57. doi: 10.1345/aph.1Q677. Epub 2012 Oct 2. [Article]
  4. Stover PJ, Field MS: Trafficking of intracellular folates. Adv Nutr. 2011 Jul;2(4):325-31. doi: 10.3945/an.111.000596. Epub 2011 Jun 28. [Article]
  5. Allegra CJ, Chabner BA, Drake JC, Lutz R, Rodbard D, Jolivet J: Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem. 1985 Aug 15;260(17):9720-6. [Article]
  6. Kovoor PA, Karim SM, Marshall JL: Is levoleucovorin an alternative to racemic leucovorin? A literature review. Clin Colorectal Cancer. 2009 Oct;8(4):200-6. doi: 10.3816/CCC.2009.n.034. [Article]
KEGG Drug
D07986
KEGG Compound
C03479
PubChem Compound
6006
PubChem Substance
46505436
ChemSpider
5784
BindingDB
50239970
RxNav
6313
ChEBI
15640
ChEMBL
CHEMBL1679
Therapeutic Targets Database
DAP001244
PharmGKB
PA450198
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Folinic_acid
AHFS Codes
  • 92:12.00 — Antidotes
FDA label
Download (2.95 MB)
MSDS
Download (72.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMalignant Neoplasm of Stomach / Stage IV Colorectal Cancer1
4CompletedTreatmentColorectal Cancers1
4CompletedTreatmentColorectal Cancers / Cytokine-Induced Killer Cells / Postoperative Complications / Survival1
4CompletedTreatmentNeoplasms, Colorectal1
4CompletedTreatmentStage-Ⅱ Colorectal Cancer1
4RecruitingTreatmentAdenocarcinoma Of Esophagus / Gastric Adenocarcinoma / Stage IIB Gastric Cancer / Stage IIIA Esophageal Adenocarcinoma / Stage IIIA Gastric Cancer / Stage IIIB Esophageal Adenocarcinoma / Stage IIIB Gastric Cancer / Stage IIIC Esophageal Adenocarcinoma / Stage IIIC Gastric Cancer1
4RecruitingTreatmentRecurrent or Metastatic Colorectal Cancer1
4RecruitingTreatmentToxoplasmosis1
4TerminatedHealth Services ResearchMalignant Neoplasm of Colon / Unresectable Metastasis Originating in Colonic Cancer1
4Unknown StatusTreatmentMetastatic Colorectal Cancer (MCRC)1

Pharmacoeconomics

Manufacturers
  • Hospira inc
  • Abic ltd
  • Abraxis pharmaceutical products
  • Bedford laboratories div ben venue laboratories inc
  • Elkins sinn div ah robins co inc
  • Pharmachemie bv
  • Pharmachemie usa inc
  • Teva parenteral medicines inc
  • App pharmaceuticals llc
  • Luitpold pharmaceuticals inc
  • Glaxosmithkline
  • Barr pharmaceuticals
  • Corepharma llc
  • Par pharmaceutical inc
  • Roxane laboratories inc
  • Sandoz inc
  • Xanodyne pharmaceutics inc
  • Spectrum pharmaceuticals inc
Packagers
  • APP Pharmaceuticals
  • Atlantic Biologicals Corporation
  • Barr Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bigmar Bioren Pharmaceuticals Sa
  • Hospira Inc.
  • Major Pharmaceuticals
  • Physicians Total Care Inc.
  • Qualitest
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
Dosage Forms
FormRouteStrength
PowderIntramuscular; Intravenous350 mg
TabletOral15 mg
Injection, solutionParenteral10 MG/ML
InjectionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous10 mg/1mL
SolutionIntramuscular; Intravenous
SolutionParenteral
CapsuleOral
Injection, solutionParenteral100 mg/10mL
Injection, solutionParenteral1000 mg/100mL
Injection, solutionParenteral300 mg30mL
Injection, solutionParenteral500 mg/50mL
Injection, solutionParenteral800 mg/80mL
Injection, solutionParenteral100 MG
Injection, solutionParenteral500 MG
Injection, solutionParenteral
InjectionParenteral10 MG/ML
Injection, solutionParenteral10 MG
Injection, powder, for solution
Powder, for solutionOral
SolutionParenteral15 mg
Injection, solution10 mg/1ml
TabletOral
Capsule, delayed release pelletsOral
Injection, powder, for solutionIntramuscular; Intravenous
SolutionOral
Injection, solutionParenteral1000 MG
Injection, solutionParenteral200 MG
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous50 mg
Injection, powder, for solutionIntravenous
Injection, solutionIntramuscular; Intravenous
TabletOral5 mg
Powder, for solutionIntramuscular; Intravenous350 mg / vial
Powder, for solutionIntramuscular; Intravenous50 mg / vial
LiquidIntramuscular; Intravenous10 mg / mL
Injection, powder, for solutionIntramuscular; Intravenous10 mg/1mL
Injection, powder, for solutionIntramuscular; Intravenous20 mg/1mL
LiquidIntravenous10 mg / mL
InjectionIntramuscular; Intravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous100 mg/10mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous200 mg/20mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous350 mg/17.5mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous50 mg/5mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous500 mg/50mL
Injection, powder, lyophilized, for suspensionIntramuscular; Intravenous100 mg/10mL
Injection, powder, lyophilized, for suspensionIntramuscular; Intravenous200 mg/20mL
Injection, powder, lyophilized, for suspensionIntramuscular; Intravenous350 mg/17.5mL
TabletOral10 mg/1
TabletOral15 mg/1
TabletOral25 mg/1
TabletOral5 mg/1
SolutionIntramuscular; Intravenous10 mg / mL
SolutionIntravenous1000 mg / 100 mL
SolutionIntravenous200 mg / 20 mL
SolutionIntravenous10 mg / mL
Powder, for solutionOral
Injection
InjectionParenteral100 MG
Injection, solutionParenteral300 MG
Injection, solutionParenteral400 MG
InjectionParenteral500 MG
InjectionParenteral900 MG
KitOral
Tablet, chewableOral
CapsuleOral
Injection, solutionParenteral900 mg
Injection, solutionParenteral50 MG
Injection, solutionParenteral50 MG/ML
Injection, powder, for solutionParenteral
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous
Injection, powder, lyophilized, for solutionIntravenous
TabletOral
SolutionOral
Injection, solution
Solution50 mg/1ml
Solution10 mg/1ml
Prices
Unit descriptionCostUnit
Leucovorin calcium 25 mg tablet24.73USD tablet
Leucovorin calcium 500 mg vial24.42USD vial
Leucovorin calcium 200 mg vial14.4USD vial
Leucovorin calcium 350 mg vial11.86USD vial
Leucovorin Calcium 10 mg/ml10.93USD ml
Leucovorin calcium 15 mg tablet10.61USD tablet
Leucovorin calcium 10 mg tablet7.69USD tablet
Lederle Leucovorin Calcium 5 mg Tablet6.85USD tablet
Leucovorin calcium 100 mg vial6.0USD vial
Leucovorin calcium 50 mg vial3.6USD vial
Leucovorin calcium 5 mg tablet2.05USD tablet
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Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)245 ºCNot Available
water solubilityCompleteNot Available
logP-3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.297 mg/mLALOGPS
logP-0.46ALOGPS
logP-2.3ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.47ChemAxon
pKa (Strongest Basic)2.81ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.66 m3·mol-1ChemAxon
Polarizability46.33 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.5642
Blood Brain Barrier-0.7779
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7344
P-glycoprotein inhibitor INon-inhibitor0.918
P-glycoprotein inhibitor IINon-inhibitor0.984
Renal organic cation transporterNon-inhibitor0.8708
CYP450 2C9 substrateNon-substrate0.7887
CYP450 2D6 substrateNon-substrate0.814
CYP450 3A4 substrateNon-substrate0.5852
CYP450 1A2 substrateNon-inhibitor0.8748
CYP450 2C9 inhibitorNon-inhibitor0.9123
CYP450 2D6 inhibitorNon-inhibitor0.9326
CYP450 2C19 inhibitorNon-inhibitor0.8984
CYP450 3A4 inhibitorNon-inhibitor0.9475
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9292
Ames testNon AMES toxic0.7955
CarcinogenicityNon-carcinogens0.9361
BiodegradationNot ready biodegradable0.8534
Rat acute toxicity2.4254 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9283
hERG inhibition (predictor II)Non-inhibitor0.5331
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate activity was demonstrated in vitro using human OAT3 expressed on HEK293 cells, while inhibitory action was observed using mouse OAT3 expressed on CHO cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]

Drug created on June 13, 2005 13:24 / Updated on June 12, 2021 01:53