LEUCOVORIN CALCIUM

First approved in 1952

Details

Stereochemistry	EPIMERIC
Molecular Formula	C20H21N7O7.Ca
Molecular Weight	511.501
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Ca++].NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)N2C=O)N1

InChI

InChIKey=KVUAALJSMIVURS-ZEDZUCNESA-L

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

HIDE SMILES / InChI

Molecular Formula	Ca
Molecular Weight	40.078
Charge	2
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C20H21N7O7
Molecular Weight	471.4234
Charge	-2
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	1 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://chemocare.com/chemotherapy/drug-info/Leucovorin.aspx

Leucovorin is a compound similar to folic acid, which is a necessary vitamin. It has been around and in use for many decades. Leucovorin is a medication frequently used in combination with the chemotherapy drugs fluoruracil and methotrexate. Leucovorin is not a chemotherapy drug itself, however it is used in addition to these chemotherapy drugs to enhance anticancer effects (with fluorouracil) or to help prevent or lessen side effects (with methotrexate). Leucovorin is also used by itself to treat certain anemia problems when folic acid deficiency is present.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 33 Target ID: P04818 Gene ID: 7298.0 Gene Symbol: TYMS Target Organism: Homo sapiens (Human) Sources: https://www.cancercare.on.ca/CCO_DrugFormulary/Pages/DfPdfContent.aspx?itemId=93949.	Inhibitor 8504
Dihydrofolate reductase 61 Target ID: P00374 Gene ID: 1719.0 Gene Symbol: DHFR Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/2260989	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Osteosarcoma 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Secondary	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953
Megaloblastic anemia 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Palliative	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953
Advanced colorectal cancer 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Palliative	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953

C_max

Value	Dose	Co-administered	Analyte	Population
391 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LEUCOVORIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
258 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
226 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
360 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		LEUCOVORIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
96 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
51 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / 5 weeks other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1810 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
65.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LEUCOVORIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.4 mg × min/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
71 mM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
364 mM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / 5 weeks other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		LEUCOVORIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg/m2 1 times / week multiple, intravenous MTD Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	Other AEs: Neurotoxicity, Diarrhea... Other AEs: Neurotoxicity (grade 1, 83.3%) Diarrhea (grade 1, 66.7%) Diarrhea (grade 3, 16.7%) Nausea (grade 1, 16.7%) Nausea (grade 2, 33.3%) Vomiting (grade 1, 33.3%) Vomiting (grade 2, 16.7%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (20%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 40%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 33.3%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 60.5 years Health Status: unhealthy Age Group: Median age 60.5 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 33.3%) Vomiting (grade 3, 33.3%) Diarrhea (grade 3, 33.3%) Paresthesia (grade 3, 33.3%) Febrile neutropenia (grade 4, 33.3%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 499 MRP3 246 MRP4 290 OATP1B1 1079 OATP1B3 961 BSEP 550	MRP3 58 MRP4 91	MRP2 146

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP2 625	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP3 326	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP4 345	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP2 625	inducer 1966 Sources: https://pubs.acs.org/doi/pdf/10.1021/jm7015683#page=3 Page: -	no
OATP1B1 1095	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP3 58	substrate 4014 Sources: https://cancerres.aacrjournals.org/content/61/19/7225.full-text.pdf Page: -	no [Km 1740 uM]
MRP4 91	substrate 4014 Sources: https://cancerres.aacrjournals.org/content/62/11/3144.full-text.pdf#page=4 Page: -	no [Km 640 uM]

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1408	http://www.3bsc.com/index/pro_info.php?id=55124
abcr GmbH	AB524413	http://www.abcr.com/shop/en/AB524413
Achemtek	0102-026003	http://www.achemtek.com/58-05-9
AEchem Scientific Corp., USA	AE045500	http://www.aechemsc.com/info_products/AE045500.php
AHH Chemical co.,ltd	MT-53184	http://www.ahhchemical.com/product/MT-53184.html
Alsachim	4281	http://www.alsachim.com/product-C5599-glo.bal-view.html
Aurora Fine Chemicals LLC	A24.077.515	http://online.aurorafinechemicals.com/info?ID=A24.077.515
BLD Pharm	BD105751	http://www.bldpharm.com/products/58-05-9.html
Boerchem	BC206228	http://www.boerchem.com/?product_34779.html
Chem Scene	CS-2989	http://www.chemscene.com/58-05-9.html
ChemMol	30103057	http://www.chemmol.com/chemmol/30103057.html
ChemMol	44002424	http://www.chemmol.com/chemmol/44002424.html
Chemspace	CSSB00102462341	https://chem-space.com/CSSB00102462341
Combi-Blocks	QW-7315	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-7315
CSNpharm	CSN10090	https://www.csnpharm.com/products/folinic-acid.html
eNovation Chemicals	D671707	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671707
eNovation Chemicals	D783523	https://www.enovationchem.com/ProductDetails.asp?ProductID=D783523
Hairui	HR129597	http://www.hairuichem.com/en/product/58-05-9.html
Lab Network	LN01296494	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01296494
MedChem Express	HY-17556	https://www.medchemexpress.com/folinic-acid.html
MuseChem	I001836	https://www.musechem.com/product/I001836.html
Selleck Chemicals	S5790	http://www.selleckchem.com/products/folinic-acid.html
Yuhao Chemical	LL0016	http://www.chemyuhao.com/58-05-9.html

PubMed

Title	Date	PubMed
Discoloration of the nails and early anemia after mitoxantrone, folinic acid and 5-fluorouracil.	1990	2283895
5-Fluorouracil-induced Raynaud's phenomenon.	1998 Nov	10023329
Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.	1999 Mar-Apr	10206466
A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma.	2001 Nov	11822757
Phase I and pharmacokinetic study of two different schedules of oxaliplatin, irinotecan, Fluorouracil, and leucovorin in patients with solid tumors.	2003 Oct 15	12963697
Methotrexate-induced leukoencephalopathy reversed by aminophylline and high-dose folinic acid.	2004	15153718
A new perspective on cardiotoxicity of 5-fluorouracil. A novel research tool 'cardiac ultrasonic integrated backscatter analysis' indicates transient, subclinical myocardial dysfunction due to high-dose leucovorin and infusional 5-fluorouracil regimen.	2004 Jun	15272225
Influence of high-dose leucovorin and 5-fluorouracil chemotherapy regimen on P wave duration and dispersion.	2004 Jun	15153089
Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the Pediatric Oncology Group 9605 protocol.	2005 Feb	15794179
Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1.	2005 Oct 1	16098483
Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature.	2005 Sep	16164401
Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.	2007 Apr	17454858
Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter.	2007 Aug	17475902
First clinical experience of orally active epidermal growth factor receptor inhibitor combined with simplified FOLFOX6 as first-line treatment for metastatic colorectal cancer.	2007 Aug 15	17594712
A Phase II study of oxaliplatin with low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) for gastric cancer patients with malignant ascites.	2007 Dec	18211984
A phase II trial of weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in patients with chemotherapy-pretreated metastatic breast cancer.	2007 Jan-Feb	17348454
Early recognition of renal toxicity of high-dose methotrexate therapy: a case report.	2008 Dec	19131789
Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response.	2008 Dec 15	19088045
An unusual presentation of hand-foot syndrome at the hidden area: the scrotum and penis.	2009	19330576
[A case of therapy for bevacizumab-induced hypertension].	2009 Jan	19151582
Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment.	2009 Jan	18976724
Second-line therapy in refractory pancreatic cancer. results of a phase II study.	2009 Mar	19295247
Acute methotrexate neurotoxicity with choreiform movements and focal neurological deficits: a case report.	2009 Oct	19738521
Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure.	2009 Oct-Nov	19863208
Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases.	2010 Dec	21208846
A phase I study of 5-fluorouracil/leucovorin and arsenic trioxide for patients with refractory/relapsed colorectal carcinoma.	2010 Jun 1	20501625
Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.	2010 May	19821069
Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.	2010 Nov	20180123
Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.	2011 Feb 11	21310276
Methotrexate-induced bone marrow adiposity is mitigated by folinic acid supplementation through the regulation of Wnt/β-catenin signalling.	2015 Mar	25187349

Patents

Sample Use Guides

In Vivo Use Guide

200 mg/m2 or 20 mg/m2 in Advanced Colorectal Cancer, 10 mg/m2 in Leucovorin Rescue After High-Dose Methotrexate Therapy and up to 1 mg daily in Megaloblastic Anemia Due to Folic Acid Deﬁciency.

Route of Administration: Intravenous

In Vitro Use Guide

RPMI 1788 cells revealed a high intrinsic resistance to methotrexate (MTX). The cytotoxic effect of high concentrations of MTX (10 -5 M) was reversed by relatively low (10 -6 M) concentrations of simultaneously added leucovorin (LV). The enhancement of cell survival was less marked when LV application was delayed for 12 h.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:17:13 GMT 2025` Edited by `admin` on `Mon Mar 31 21:17:13 GMT 2025`
Record UNII	RPR1R4C0P4
Record Status	`Validated (UNII)`
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Name

Type

Language

LEUCOVORIN CALCIUM

Common Name

English

CALCIUM FOLINATE

Preferred Name

English

Calcium folinate [WHO-DD]

Common Name

English

FOLIC ACID RELATED COMPOUND A

Common Name

English

LEUCOVORIN CALCIUM [VANDF]

Common Name

English

NSC-3590

Code

English

CALCIUM FOLINATE [VANDF]

Common Name

English

FOLINIC ACID (AS CALCIUM FOLINATE)

Common Name

English

Folfox component leucovorin calcium

Common Name

English

CALCIUM N-(P-((((6RS)-2-AMINO-5-FORMYL-5,6,7,8-TETRAHYDRO-4-HYDROXY-6-PTERIDINYL)METHYL)AMINO)BENZOYL)-L-GLUTAMATE (1:1)

Common Name

English

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)

Common Name

English

CALCIUM FOLINATE [MART.]

Common Name

English

calcium folinate [INN]

Common Name

English

ANHYDROUS CALCIUM FOLINATE

Common Name

English

LEUCOVORIN CALCIUM [USP MONOGRAPH]

Common Name

English

CALCIUM FOLINATE [EP IMPURITY]

Common Name

English

LEUCOVORIN CALCIUM [USP-RS]

Common Name

English

LEUCOVORIN CALCIUM [ORANGE BOOK]

Common Name

English

FOLIC ACID RELATED COMPOUND A [USP-RS]

Common Name

English

CALCIUM FOLINATE [JAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

V03AF03