请输入您要查询的百科知识:

 

词条 Folinic acid
释义

  1. Medical use

  2. Side effects

  3. Drug interactions

  4. Mechanism of action

  5. History

  6. Names

  7. References

  8. External links

{{Distinguish|folic acid}}{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 470454241
| IUPAC_name = (2S)-2-{[4-[(2-amino-5-formyl-4-oxo-5,6,7,8-
tetrahydro-1H-pteridin-6-yl)methylamino]
benzoyl]amino}pentanedioic acid
| image = Folinic acid.svg
| alt = Skeletal formula of folinic acid
| width = 250
| image2 = Leucovorin molecule ball.png
| alt2 = Ball-and-stick model of the folinic acid molecule
| synonyms = citrovorum factor, 5-formyltetrahydrofolate
| pronounce = Leucovorin {{IPAc-en|ˌ|lj|uː|k|oʊ|ˈ|v|ɔː|r|ɪ|n}}
| tradename = Many
| Drugs.com = {{drugs.com|monograph|leucovorin-calcium}}
| pregnancy_AU = A
| pregnancy_US = C
| legal_status = Rx-only
| routes_of_administration = intravenous, IM, by mouth
| bioavailability = Dose dependent
| protein_bound = ~15%
| metabolism =
| elimination_half-life = 6.2 hours
| excretion = Urinary
| IUPHAR_ligand = 4816
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 1492-18-8
| ATC_prefix = V03
| ATC_suffix = AF03
| PubChem = 6006
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00650
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5784
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = RPR1R4C0P4
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1679
| C=20 | H=23 | N=7 | O=7
| molecular_weight = 473.44 g/mol
| SMILES = O=C(O)[C@@H](NC(=O)c1ccc(cc1)NCC3N(/C2=C(/N/C(=N\\C2=O)N)NC3)C=O)CCC(=O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VVIAGPKUTFNRDU-ABLWVSNPSA-N
| density =
| melting_point = 245
| melting_high =
| melting_notes = decomp
| solubility = ~0.3[1]
}}Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine.[2][3] It is also used in combination with 5-fluorouracil to treat colorectal cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning.[3][4] It is taken by mouth, injection into a muscle, or injection into a vein.[3]

Side effects may include trouble sleeping, allergic reactions, or fever.[2][3] Use in pregnancy or breastfeeding is generally regarded as safe.[2] When used for anemia it is recommended that pernicious anemia as a cause be ruled out first.[3] Folinic acid is a form of folic acid that does not require activation by dihydrofolate reductase to be useful to the body.[3]

Folinic acid was first made in 1945.[5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] In the United Kingdom it costs the NHS about 4.62 pounds per 30 mg vial.[2]

Medical use

Folinic acid is given following methotrexate as part of a total chemotherapeutic plan, where it may protect against bone marrow suppression or gastrointestinal mucosa inflammation. No apparent effect is seen on pre-existing methotrexate-induced nephrotoxicity.[7] Folinic acid can be taken as a pill (orally) or injected into a vein (intravenously) or muscle (intramuscularly).[8]

While not specifically an antidote for methotrexate, folinic acid may also be useful in the treatment of acute methotrexate overdose. Different dosing protocols are used, but folinic acid should be redosed until the methotrexate level is less than 5 x 10−8 M.[9]

Additionally, folinic acid is sometimes used to reduce the side effects of methotrexate in rheumatoid arthritis patients. This includes reductions in nausea, abdominal pain, abnormal liver blood tests, and mouth sores.[10]

Folinic acid is also used in combination with the chemotherapy agent 5-fluorouracil in treating colon cancer. In this case, folinic acid is not used for "rescue" purposes; rather, it enhances the effect of 5-fluorouracil by inhibiting thymidylate synthase.

Folinic acid is also sometimes used to prevent toxic effects of high doses of antimicrobial dihydrofolate reductase inhibitors such as trimethoprim and pyrimethamine. It may be prescribed in the treatment of toxoplasmosis retinitis, in combination with the folic acid antagonists pyrimethamine and sulfadiazine.

Folinic acid is also used in the treatment of cerebral folate deficiency, a syndrome in which the use of folic acid cannot normalize cerebrospinal fluid levels of 5-MTHF.[11]

Side effects

Folinic acid should not be administered intrathecally. This may produce severe adverse effects or even death.[12]

Drug interactions

Fluorouracil: Folinic acid may increase the toxicity associated with fluorouracil if the two are administered together. Some adverse effects that have occurred, particularly in elderly patients, include severe enterocolitis, diarrhea, and dehydration.[13]Sulfamethoxazole-trimethoprim: A potential drug interaction exists with concomitant use of sulfamethoxazole-trimethoprim and folinic acid. Folinic acid has been shown to decrease the efficacy of sulfamethoxazole-trimethoprim in the treatment of Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a common cause of pneumonia in AIDS patients.[14]

Mechanism of action

Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., 5,10-methylenetetrahydrofolate, 5-methyltetrahydrofolate), thus has vitamin activity equivalent to that of folic acid. Since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate. This is the classical view of folinic acid rescue therapy. In 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate exists. Although the mechanism is not very clear, the polyglutamylation of methotrexate and dihydrofolate in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folinic acid in normal cells.[15]

Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so some normal DNA replication processes can proceed.

Folinic acid has dextro- and levorotary isomers, only the latter one being pharmacologically useful. As such, levoleucovorin was approved by the FDA in 2008.[16]

History

Folinic acid was discovered as a needed growth factor for the bacterium Leuconostoc citrovorum in 1948, by Sauberlich and Baumann. This resulted in it being called "citrovorum factor," meaning citrovorum growth factor. It had an unknown structure, but was found to be a derivative of folate that had to be metabolized in the liver before it could support growth of L. citrovorum. The synthesis of citrovorum factor by liver cells in culture was eventually accomplished from pteroylglutamic acid in the presence of suitable concentrations of ascorbic acid. The simultaneous addition of sodium formate to such systems resulted in increased citrovorum factor activity in the cell-free supernatants (producing, as now known, the 5-formyl derivative), and from this method of preparation of large amounts of the factor, its structure as levo-folinic acid (5-formyl tetrahydrofolic acid) was eventually deduced.{{citation needed|date=February 2015}}

Names

Folinic acid should be distinguished from folic acid (vitamin B9). However, folinic acid is a vitamer for folic acid and has the full vitamin activity of this vitamin. Levofolinic acid and its salts are the 2S- form of the molecule. They are the only forms of the molecule that are known to be biologically active.

It is generally administered as the calcium or sodium salt (calcium folinate (INN), sodium folinate, leucovorin calcium, leucovorin sodium).

References

1. ^{{Cite web|url=https://www.caymanchem.com/msdss/20383m.pdf|title=Safety Data Sheet Folinic Acid (calcium salt)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=25 January 2018}}
2. ^{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=576–577|edition=69}}
3. ^{{cite web|title=Leucovorin Calcium|url=https://www.drugs.com/monograph/leucovorin-calcium.html|publisher=The American Society of Health-System Pharmacists|accessdate=8 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20170510115807/https://www.drugs.com/monograph/leucovorin-calcium.html|archivedate=10 May 2017|df=}}
4. ^{{cite book|last1=Munjal|first1=Y. P.|last2=Sharm|first2=Surendra K.|title=API Textbook of Medicine, Ninth Edition, Two Volume Set|date=2012|publisher=JP Medical Ltd|isbn=9789350250747|page=1945|url=https://books.google.ca/books?id=L7pW3yGjj7kC&pg=PA1945|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20170510215410/https://books.google.ca/books?id=L7pW3yGjj7kC&pg=PA1945|archivedate=2017-05-10|df=}}
5. ^{{cite book|last1=Sneader|first1=Walter|title=Drug Discovery: A History|date=2005|publisher=John Wiley & Sons|isbn=9780471899792|page=235|url=https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA235|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20170510233831/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA235|archivedate=2017-05-10|df=}}
6. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}}
7. ^Therapeutic Information Resources Australia (2004). Calcium Folinate (Systemic) in AUSDI: Australian Drug Information for the Health Care Professional. Castle Hill: Therapeutic Information Resources Australia.{{page needed|date=February 2015}}
8. ^{{cite journal |pmid=3257913|year=1988|author1=McGuire|first1=B. W.|title=Pharmacokinetics of leucovorin calcium after intravenous, intramuscular, and oral administration|journal=Clinical Pharmacy|volume=7|issue=1|pages=52–8|last2=Sia|first2=L. L.|last3=Leese|first3=P. T.|last4=Gutierrez|first4=M. L.|last5=Stokstad|first5=E. L.}}
9. ^{{cite web |url=http://www.cancercare.on.ca/pdfdrugs/leucovo.pdf |title=Archived copy |accessdate=2014-01-07 |deadurl=no |archiveurl=https://web.archive.org/web/20081010050826/http://www.cancercare.on.ca/pdfdrugs/Leucovo.pdf |archivedate=2008-10-10 |df= }}{{full citation needed|date=February 2015}}
10. ^{{cite journal |doi=10.1002/14651858.CD000951.pub2|pmid=23728635|title=Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis|journal=Cochrane Database of Systematic Reviews|volume=5|issue=5|pages=CD000951|year=2013|last1=Shea|first1=Beverley|last2=Swinden|first2=Michael V|last3=Tanjong Ghogomu|first3=Elizabeth|last4=Ortiz|first4=Zulma|last5=Katchamart|first5=Wanruchada|last6=Rader|first6=Tamara|last7=Bombardier|first7=Claire|last8=Wells|first8=George A|last9=Tugwell|first9=Peter}}
11. ^{{cite journal |last1=Gordon |first1=N |title=Cerebral folate deficiency. |journal=Developmental Medicine and Child Neurology |date=2009 |volume=51 |issue=3 |pages=180–182 |doi=10.1111/j.1469-8749.2008.03185.x |pmid=19260931}}
12. ^{{cite journal |doi=10.1097/00043426-199608000-00014|pmid=8689347|title=Intrathecal Leucovorin After Intrathecal Methotrexate Overdose|journal=Journal of Pediatric Hematology/Oncology|volume=18|issue=3|pages=302–4|year=1996|last1=Jardine|first1=Lawrence F.|last2=Ingram|first2=Lewis C.|last3=Bleyer|first3=W. Archie}}
13. ^{{cite journal |pmid=7627739|year=1995|author1=Trissel|first1=L. A.|title=Incompatibility of fluorouracil with leucovorin calcium or levoleucovorin calcium|journal=American Journal of Health-System Pharmacy |volume=52|issue=7|pages=710–5|last2=Martinez|first2=J. F.|last3=Xu|first3=Q. A.}}
14. ^{{cite journal |pmid=11876516|year=2002|author1=Razavi|first1=B|title=Failure of trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia with concurrent leucovorin use|journal=Infection|volume=30|issue=1|pages=41–2|last2=Lund|first2=B|last3=Allen|first3=B. L.|last4=Schlesinger|first4=L|doi=10.1007/s15010-001-1172-0}}
15. ^{{cite journal |pmid=2448654|year=1987|author1=Goldman|first1=I. D.|title=Biochemical factors in the selectivity of leucovorin rescue: Selective inhibition of leucovorin reactivation of dihydrofolate reductase and leucovorin utilization in purine and pyrimidine biosynthesis by methotrexate and dihydrofolate polyglutamates|journal=NCI Monographs |issue=5|pages=17–26|last2=Matherly|first2=L. H.}}
16. ^{{cite web |url=https://www.drugs.com/newdrugs/fda-approves-new-application-levoleucovorin-spectrum-s-first-proprietary-oncology-drug-888.html |author=Drugs.com |title=FDA Approves Levoleucovorin |date=2008-05-07 |accessdate=2009-06-07 |deadurl=no |archiveurl=https://web.archive.org/web/20090702033819/http://www.drugs.com/newdrugs/fda-approves-new-application-levoleucovorin-spectrum-s-first-proprietary-oncology-drug-888.html |archivedate=2009-07-02 |df= }}

External links

  • U.S. National Library of Medicine: Drug Information Portal – Folinic acid
{{Detoxifying agents for antineoplastic treatment}}{{Vitamin}}{{portal bar|Pharmacy and pharmacology|Medicine}}

4 : Chemotherapeutic adjuvants|Folates|World Health Organization essential medicines|RTT

随便看

 

开放百科全书收录14589846条英语、德语、日语等多语种百科知识,基本涵盖了大多数领域的百科知识,是一部内容自由、开放的电子版国际百科全书。

 

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间:2024/11/11 10:16:53