Folinic acid (Calcium)

Names

[ Name ]:
Folinic acid (Calcium)

[Synonym ]:
L-N-(p-(((2-Amino-5-formyl-5,6,7,8-tetrahydro-3-hydroxy-6-pteridinyl)methyl)amino)benzoyl)glutamic Acid Calcium Salt (1:1)
calcium, [L-glutamato(2-)-κO,κO, N-[4-[[(2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-]-
(2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydroptéridin-6-yl)méthyl]amino}phényl)carbonyl]amino}pentanedioate de calcium
[N-(4-{[(2-Amino-5-formyl-4-hydroxy-5,6,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamato(2-)-κO,O]calcium
5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic acid calcium salt
Calcium folinate
5-HCO-H4PteGlu
Leucovorin calcium salt
Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)amino]pentanedioate
MFCD00006704
Calcium-(2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)carbonyl]amino}pentandioat
Calcium Folinate Hydrate
5-Formyl-5,6,7,8-tetrahydrofolic acid calcium salt
Folinic Acid Calcium Salt Hydrate
Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-hydroxy-5,6,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)amino]pentanedioate
Leucovorin calcium
Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate
[N-(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamato(2-)-κO,O]calcium
EINECS 216-082-8
Folinic acid calcium salt
calcium (2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)carbonyl]amino}pentanedioate
(+)-L-Folinic Acid Calcium Salt
Citrovorum factor calcium salt
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)
calcium, [L-glutamato(2-)-κO,κO, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-]-
[N-(4-{[(2-Amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)-D-glutamato(2-)-κO,O]calcium
Folinic acid (Calcium)

Biological Activity

[Description]:

Leucovorin Calcium is a reduced folic acid.IC50 Value: 30 μM for zcSHMT and70 μM for zmSHMT [2]Target: Antifolatein vitro: Increasing concentrations of leucovorin (N5-CHO-THF) inhibit both zcSHMT and hcSHMT activities substantially, yet to a lesser extent than zmSHMT. The IC50 of leucovorin is approximately 30 μM for zcSHMT and higher than 70 μM for zmSHMT. The differential inhibition is evident with the presence of 10 μM leucovorin, the concentration estimated in serum in a high-dose leucovorin rescue regimen [2].in vivo: Following intravenous administration, peak plasma concentrations of (6R) LV, (6S) LV, and 5-CH3 THF were 148 +/- 32, 59.1 +/- 22, and 17.8 +/- 17 microM, respectively. During oral administration of LV, virtually no (6S) LV appeared in the plasma. Steady-state plasma concentrations of (6R) LV and 5-CH3 THF were approximately 1.5 +/- 0.23 and 2.8 +/- 0.41 microM, respectively [1]. 24 fasted subjects were given 4 of a series of 5 single test doses between 20 and 100 mg, at 1-week intervals, of 5-formyl-THF as an oral solution of leucovorin calcium. Six separate subjects received 200 mg iv and po in a 2-way crossover. Blood and urine samples were collected over 24 hours for differential microbiological folate assays using Lactobacillus casei and Streptococcus faecalis. Using L casei activity to measure total serum folates, the area under the concentration-time curve from 0 to infinite time (AUC[0-infinity]) was calculated. Relative bioavailabilities were 78%, 62%, 49%, and 42% for the 40-, 60-, 80-, and 100-mg doses, respectively [3].Clinical trial: Leucovorin and Fluorouracil With or Without SU-5416 in Treating Patients With Metastatic Colorectal Cancer . Phase 3

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Antifolate

Research Areas >> Cancer

[References]

[1]. Schilsky RL, Ratain MJ. Clinical pharmacokinetics of high-dose leucovorin calcium after intravenous and oral administration. J Natl Cancer Inst. 1990 Sep 5;82(17):1411-5.

[2]. Chang WN, Tsai JN, Chen BH, Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37.

[3]. McGuire BW, Sia LL, Haynes JD, Absorption kinetics of orally administered leucovorin calcium. NCI Monogr. 1987;(5):47-56.

[Related Small Molecules]

Chemical & Physical Properties

[ Melting Point ]:
240-250ºC

[ Molecular Formula ]:
C₂₀H₂₁CaN₇O₇

[ Molecular Weight ]:
511.501

[ Exact Mass ]:
511.112823

[ PSA ]:
198.10000

[ LogP ]:
1.41100

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MA0600500

CAS REGISTRY NUMBER :: 1492-18-8

LAST UPDATED :: 199706

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C20-H21-N7-O7.Ca

MOLECULAR WEIGHT :: 511.56

WISWESSER LINE NOTATION :: T66 BN DN GN JM&TJ CZ EQ GVH I1MR DVMYVO2VO &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >8 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1063 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >7 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1036 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 732 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,910,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6060 No. of Facilities: 103 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 3686 (estimated) No. of Female Employees: 2084 (estimated)

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H315-H317-H319-H334-H335

[ Precautionary Statements ]:
P261-P280-P305 + P351 + P338-P342 + P311

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R36/37/38;R42/43

[ Safety Phrases ]:
S26-S36-S36/37-S22

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
MA0600500

[ HS Code ]:
2942000000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2942000000