Caffeine citrate
{{Short description|Medication}}
{{Use dmy dates|date=March 2024}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 447554299
| image = Caffeine citrate.svg
| image_class = skin-invert-image
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| pronounce =
| tradename = Cafcit, Gencebok, Cafnea, others
| Drugs.com = {{drugs.com|monograph|caffeine-caffeine-and-sodium-benzoate-injection-caffeine-citrate}}
| MedlinePlus =
| DailyMedID = Caffeine_citrate
| pregnancy_AU =
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = By mouth, intravenous (IV)
| class =
| ATC_prefix = N06
| ATC_suffix = BC01
| ATC_supplemental =
| legal_AU = Unscheduled
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
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| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Gencebok Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1465.htm | access-date=3 March 2023}}
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| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 69-22-7
| CAS_supplemental =
| PubChem = 6241
| IUPHAR_ligand =
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| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6005
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = U26EO4675Q
| KEGG_Ref =
| KEGG = D07603
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref =
| ChEMBL = 1200569
| NIAID_ChemDB =
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| synonyms =
| IUPAC_name = 1,3,7-trimethylpurine-2,6-dione; 2-hydroxypropane-1,2,3-tricarboxylic acid
| C = 14
| H = 18
| N = 4
| O = 9
| SMILES = CN1C=NC2=C1C(=O)N(C(=O)N2C)C.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H10N4O2.C6H8O7/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2;7-3(8)1-6(13,5(11)12)2-4(9)10/h4H,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RCQXSQPPHJPGOF-UHFFFAOYSA-N
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Caffeine citrate, sold under the brand name Cafcit among others, is a medication used to treat a lack of breathing in premature babies. Specifically it is given to babies who are born at less than 35 weeks or weigh less than {{convert|2|kg|lb}} once other causes are ruled out.{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | page = 485}} It is given by mouth or slow injection into a vein.{{cite web|title=Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate|url=https://www.drugs.com/monograph/caffeine-caffeine-and-sodium-benzoate-injection-caffeine-citrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170716044142/https://www.drugs.com/monograph/caffeine-caffeine-and-sodium-benzoate-injection-caffeine-citrate.html|archive-date=16 July 2017}}
Side effects can include problems feeding, increased heart rate, low blood sugar, necrotizing enterocolitis, and kidney problems. Testing blood caffeine levels is occasionally recommended. Although it is often referred to as a citric acid salt of caffeine,{{cite book| vauthors = Donn SM, Sinha SK |title=Manual of Neonatal Respiratory Care|date=2012|publisher=Springer Science & Business Media|isbn=9781461421559|page=457|url=https://books.google.com/books?id=9rnVSufZFFwC&pg=PA457|language=en|url-status=live|archive-url=https://web.archive.org/web/20161230000058/https://books.google.ca/books?id=9rnVSufZFFwC&pg=PA457|archive-date=30 December 2016}} as implied by its name, caffeine citrate in fact consists of cocrystals of the two components. Caffeine citrate is in the xanthine family of medication. It works by stimulating the respiratory centers in the brain.
Caffeine was discovered in 1819.{{cite book| vauthors = Brown N |title=In Silico Medicinal Chemistry: Computational Methods to Support Drug Design|date=2015|publisher=Royal Society of Chemistry|isbn=9781782621638|page=20|url=https://books.google.com/books?id=kLfbCgAAQBAJ&pg=PA20|language=en|url-status=live|archive-url=https://web.archive.org/web/20161229171147/https://books.google.ca/books?id=kLfbCgAAQBAJ&pg=PA20|archive-date=29 December 2016}} It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }} The intravenous form may also be taken by mouth.{{cite book| vauthors = Ainsworth SB |title=Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life|date=2014|publisher=John Wiley & Sons|isbn=9781118819517|page=120|edition=7|url=https://books.google.com/books?id=EORvBAAAQBAJ&pg=PA120|language=en|url-status=live|archive-url=https://web.archive.org/web/20161230002108/https://books.google.ca/books?id=EORvBAAAQBAJ&pg=PA120|archive-date=30 December 2016}}
In June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of Gencebok.{{cite web | title=Gencebok: Pending EC decision | website=European Medicines Agency (EMA) | date=25 June 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/gencebok | access-date=26 June 2020 | archive-date=27 June 2020 | archive-url=https://web.archive.org/web/20200627010758/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/gencebok | url-status=dead }} It was approved for use in the European Union in August 2020.{{cite web | title=Gencebok EPAR | website=European Medicines Agency (EMA) | date=19 June 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/gencebok | access-date=27 August 2020}}
Medical uses
Caffeine citrate is generally the preferred treatment for apnea of prematurity for infants born 28 to 32 weeks or earlier than 28 weeks.{{Cite web |date=2 April 2020 |title=NIH-funded research leads to pediatric labeling updates for doxycycline, clindamycin and caffeine citrate |url=https://www.nih.gov/news-events/news-releases/nih-funded-research-leads-pediatric-labeling-updates-doxycycline-clindamycin-caffeine-citrate |access-date=27 July 2022 |website=National Institutes of Health (NIH) |language=EN}} It has fewer side effects as compared to theophylline.
Caffeine improves airway function in asthma, increasing forced expiratory volume (FEV1) by 5% to 18%, with this effect lasting for up to four hours.{{cite journal | vauthors = Welsh EJ, Bara A, Barley E, Cates CJ | title = Caffeine for asthma | journal = The Cochrane Database of Systematic Reviews | volume = 2010 | issue = 1 | pages = CD001112 | date = January 2010 | pmid = 20091514 | pmc = 7053252 | doi = 10.1002/14651858.CD001112.pub2 }}
Mechanism
In method of action, the preparation is identical to that of caffeine base as the citrate counter ion dissociates in water. Doses of caffeine citrate, due to the added weight of the citrate moiety, are understandably higher than with caffeine base, i.e., it takes a larger dose to get the same amount of caffeine. The ratio of therapeutic doses of caffeine base to its citrate salt is typically 1:2. Dosing should therefore be clearly distinguished.
Manufacture
The drug is prepared by combining anhydrous caffeine with citric acid monohydrate and sodium citrate dihydrate. Caffeine citrate cocrystals can take on at least two anhydrous polymorphs.{{Cite journal| vauthors = Smit JP, Hagen EJ |date=1 March 2015|title=Polymorphism in Caffeine Citric Acid Cocrystals|url=|journal=Journal of Chemical Crystallography|volume=45|issue=3|pages=128–133|doi=10.1007/s10870-015-0573-3|s2cid=96712417|issn=1572-8854}}
References
{{Reflist}}
External links
- {{cite web | title=Caffeine Citrate (CUI C0054436) | website=NCI Metathesaurus | url=https://ncimeta.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary=NCI%20MetaThesaurus&code=C0054436 }}
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Category:Adenosine receptor antagonists
Category:World Health Organization essential medicines