Synonym
Folinic acid calcium salt pentahydrate; Leucovorin calcium hydrate;
IUPAC/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
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
SMILES Code
O=C([O-])CC[C@@H](C([O-])=O)NC(C1=CC=C(NCC2N(C=O)C3=C(NC(N)=NC3=O)NC2)C=C1)=O.[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[Ca+2]
Appearance
white to light yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Folinic acid calcium salt pentahydrate (Leucovorin calcium salt pentahydrate) is generally administered along with methotrexate (MTX) as a rescue agent to decrease MTX-induced toxicity.
In vitro activity:
As LV (Leucovorin) can abrogate antifolate toxicity, this study next examined if efficacy of PDX would be compromised by the addition of LV 24 h later. H2052 cells were treated with antifolate as before, but media containing 2μM LV was added for another 24 h period, followed by removal of drugs and culture in fresh media for a further 48 h. The addition of 2μM LV raised the IC50 slightly for MTX and pemetrexed (Fig. 2d).
Reference: Cancer Chemother Pharmacol. 2014; 74(5): 1029–1032. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209237/v
In vivo activity:
The effect of LV (Leucovorin) treatment on PDX efficacy and toxicity was examined using H2052 xenografts in nude mice (Fig. 3). Using 60 mg/kg as the equivalent clinical dose, tumor regression was seen both with and without LV treatment in this cohort. Efficacy was nearly identical, but mice that were treated with LV had less toxicity and bodyweight remained close to control animals.
Reference: Cancer Chemother Pharmacol. 2014; 74(5): 1029–1032. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209237/v
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| Water |
10.0 |
16.62 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
601.58
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Tedeschi PM, Kathari YK, Farooqi IN, Bertino JR. Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts. Cancer Chemother Pharmacol. 2014 Nov;74(5):1029-32. doi: 10.1007/s00280-014-2580-z. Epub 2014 Sep 9. PMID: 25205429; PMCID: PMC4209237.
In vitro protocol:
1. Tedeschi PM, Kathari YK, Farooqi IN, Bertino JR. Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts. Cancer Chemother Pharmacol. 2014 Nov;74(5):1029-32. doi: 10.1007/s00280-014-2580-z. Epub 2014 Sep 9. PMID: 25205429; PMCID: PMC4209237.
In vivo protocol:
1. Tedeschi PM, Kathari YK, Farooqi IN, Bertino JR. Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts. Cancer Chemother Pharmacol. 2014 Nov;74(5):1029-32. doi: 10.1007/s00280-014-2580-z. Epub 2014 Sep 9. PMID: 25205429; PMCID: PMC4209237.
1: Schwartzman AD, Sethi R, Smith R. Multiorgan failure in a patient treated with the 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan regimen. Clin Colorectal Cancer. 2013 Jun;12(2):136-9. doi: 10.1016/j.clcc.2012.09.005. Epub 2012 Oct 24. Review. PubMed PMID: 23098664.
2: 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. Review. PubMed PMID: 23032661.
3: 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. Review. PubMed PMID: 19822510.
4: Sterba J, ValÃk D, Bajciová V, Kadlecová V, Gregorová V, Mendelová D. High-dose methotrexate and/or leucovorin rescue for the treatment of children with lymphoblastic malignancies: do we really know why, when and how? Neoplasma. 2005;52(6):456-63. Review. PubMed PMID: 16284689.
5: Kauh J, Johnstone P. Commentary on Wang et al., "Pre-operative chemotherapy with oral tegafur-uracil and leucovorin for rectal cancer" (J Surg Oncol 89: 256-263). J Surg Oncol. 2005 May 1;90(2):106-7. Review. PubMed PMID: 15844186.
6: Hwang JJ. Irinotecan and 5-FU/ leucovorin in metastatic colorectal cancer: balancing efficacy, toxicity, and logistics. Oncology (Williston Park). 2004 Dec;18(14 Suppl 14):26-34. Review. PubMed PMID: 15685831.
7: André T, Noirclerc M, Hammel P, Meckenstock R, Landi B, Cattan S, Selle F, Codoul JF, Guerrier-Parmentier B, Mokhtar R, Louvet C; GERCOR. Phase II study of leucovorin, 5-fluorouracil and gemcitabine for locally advanced and metastatic pancreatic cancer (FOLFUGEM 2). Gastroenterol Clin Biol. 2004 Aug-Sep;28(8-9):645-50. Review. PubMed PMID: 15646530.
8: Reddy GK. Intergroup trial fails to demonstrate a benefit with the addition of irinotecan to bolus 5-fluorouracil/leucovorin in stage III colon cancer. Clin Colorectal Cancer. 2004 Nov;4(4):230-2. Review. PubMed PMID: 15555203.
9: Di Leo A, Buyse M, Bleiberg H. Is overall survival a realistic primary end point in advanced colorectal cancer studies? A critical assessment based on four clinical trials comparing fluorouracil plus leucovorin with the same treatment combined either with oxaliplatin or with CPT-11. Ann Oncol. 2004 Apr;15(4):545-9. Review. PubMed PMID: 15033657.
10: Hwang JJ, Eisenberg SG, Marshall JL. Improving the toxicity of irinotecan/5-FU/leucovorin: a 21-day schedule. Oncology (Williston Park). 2003 Sep;17(9 Suppl 8):37-43. Review. PubMed PMID: 14569847.
11: Saad ED, Hoff PM. UFT and oral leucovorin as radiation sensitizers in rectal and other gastrointestinal malignancies. Cancer Invest. 2003;21(4):624-9. Review. PubMed PMID: 14533450.
12: Kuebler JP, de Gramont A. Recent experience with oxaliplatin or irinotecan combined with 5-fluorouracil and leucovorin in the treatment of colorectal cancer. Semin Oncol. 2003 Aug;30(4 Suppl 15):40-6. Review. PubMed PMID: 14523794.
13: Ghosh A, Boyd R. Leucovorin (calcium folinate) in "antifreeze" poisoning. Emerg Med J. 2003 Sep;20(5):466. Review. PubMed PMID: 12954693; PubMed Central PMCID: PMC1726214.
14: Twelves C. Can capecitabine replace 5-FU/leucovorin in combination with oxaliplatin for the treatment of advanced colorectal cancer? Oncology (Williston Park). 2002 Dec;16(12 Suppl No 14):23-6. Review. PubMed PMID: 12520636.
15: Fisher MD. Irinotecan/5-FU/leucovorin, oxaliplatin/5-FU/leucovorin, and oxaliplatin/irinotecan are each effective in the treatment of 5-FU-resistant advanced colorectal cancer. Clin Colorectal Cancer. 2001 Aug;1(2):85-6. Review. PubMed PMID: 12445365.
16: Fisher MD. Recommendation for irinotecan, 5-fluorouracil, and leucovorin as first-line therapy for colorectal cancer. Clin Colorectal Cancer. 2001 Aug;1(2):82-4. Review. PubMed PMID: 12445364.
17: Langer CJ. The role of UFT and the combination of UFT/leucovorin in non-small cell lung cancer. Lung Cancer. 2001 Nov;34(2):297-303. Review. PubMed PMID: 11679189.
18: Minsky BD. UFT plus oral leucovorin calcium (Orzel) and radiation in combined modality therapy: a comprehensive review. Int J Cancer. 2001 Feb 20;96(1):1-10. Review. PubMed PMID: 11241325.
19: Douillard JY; V-303 Study Group. Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. Oncology (Williston Park). 2000 Dec;14(12 Suppl 14):51-5. Review. PubMed PMID: 11200150.
20: Hoff PM. The tegafur-based dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines, UFT/leucovorin (ORZEL) and S-1: a review of their clinical development and therapeutic potential. Invest New Drugs. 2000 Nov;18(4):331-42. Review. PubMed PMID: 11081569.
