| 词条 | Cidofovir |
| 释义 |
| verifiedrevid = 477165826 | IUPAC_name = ({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid | image = Cidofovir.svg | width = 225 | tradename = Vistide | Drugs.com = {{drugs.com|monograph|cidofovir}} | licence_EU = yes | licence_US = Cidofovir | pregnancy_AU = D | pregnancy_US = C | legal_AU = S4 | legal_CA = Rx-only | legal_UK = POM | legal_US = Rx-only | routes_of_administration = IV | bioavailability = complete | protein_bound = <6% | elimination_half-life = 2.6 hours (active metabolites: 15-65 hours) | excretion = renal The above pharmacokinetic parameters are measured for cidofovir used in conjunction with probenecid.[1] | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 113852-37-2 | ATC_prefix = J05 | ATC_suffix = AB12 | ATC_supplemental = | PubChem = 60613 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00369 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 54636 | NIAID_ChemDB = 001049 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 768M1V522C | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 3696 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 152 | C=8 | H=14 | N=3 | O=6 | P=1 | molecular_weight = 279.187 g/mol | smiles = O=C1/N=C(\\C=C/N1C[C@H](OCP(=O)(O)O)CO)N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VWFCHDSQECPREK-LURJTMIESA-N | melting_point = 260 | specific_rotation = -97.3 }}Cidofovir (brand name Vistide) is an injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis (an infection of the retina of the eye) in people with AIDS.[2][3] Cidofovir was approved for medical use in 1996.[2] Medical useDNA virusIts only indication that has received regulatory approval worldwide is cytomegalovirus retinitis.[2][3] Cidofovir has also shown efficacy in the treatment of aciclovir-resistant HSV infections.[3] Cidofovir has also been investigated as a treatment for progressive multifocal leukoencephalopathy with successful case reports of its use.[4] Despite this, the drug failed to demonstrate any efficacy in controlled studies.[5] Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of a bioterror incident involving smallpox cases.[6] Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.[7] It has inhibitory effects on varicella-zoster virus replication in vitro although no clinical trials have been done to date, likely due to the abundance of safer alternatives such as aciclovir.[8] Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients.[9] Cidofovir is being investigated as a complementary intralesional therapy against papillomatosis caused by HPV.[10][11] It first received FDA approval on 26 June 1996,[12] TGA approval on 30 April 1998[3] and EMA approval on 23 April 1997.[13] It has been used topically to treat warts.[14] OtherIt has been suggested as an antitumour agent, due to its suppression of FGF2.[15][16] AdministrationCidofovir is only available as an intravenous formulation. Cidofovir is to be administered with probenecid which decreases side effects to the kidney.[17] Probenecid mitigate nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.[18] In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir.[17] Side effectsThe major dose-limiting side effect of cidofovir is nephrotoxicity (that is, kidney damage).[19] Other common side effects (occurring in >1% of people treated with the drug) include:[20][19] {{div col|colwidth=18em}}
Whereas uncommon side effects include: anaemia and elevated liver enzymes and rare side effects include: tachycardia and Fanconi syndrome.[19] Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.[21] ContraindicationsHypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity).[20] InteractionsIt is known to interact with nephrotoxic agents (e.g. amphotericin B, foscarnet, IV aminoglycosides, IV pentamide, vancomycin, tacrolimus, non-steroid anti-inflammatory drugs, etc.) to increase their nephrotoxic potential.[20][22] As it must be given concurrently with probenecid it is advised that drugs that are known to interact with probenecid (e.g. drugs that probenecid interferes with the renal tubular secretion of, such as paracetamol, aciclovir, aminosalicylic acid, etc.) are also withheld.[22] Mechanism of actionIts active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral DNA polymerases.[22] It also inhibits human polymerases but this action is 8-600 times weaker than its actions on viral DNA polymerases.[22] It also incorporates itself into viral DNA hence inhibiting viral DNA synthesis during reproduction.[22] It possesses in vitro activity against the following viruses:[23]
HistoryCidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences[24] and is marketed with the brand name Vistide by Gilead in the USA, and by Pfizer elsewhere. SynthesisCidofovir can be synthesized from a pyrimidone derivative and a protected derivative of glycidol.[25] See also
References1. ^Cundy, Kenneth C. "Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir." Clinical Pharmacokinetics 36.2 (1999): 127-43. {{Antivirals}}2. ^{{cite book|last1=Long|first1=Sarah S.|last2=Pickering|first2=Larry K.|last3=Prober|first3=Charles G.|title=Principles and Practice of Pediatric Infectious Disease|date=2012|publisher=Elsevier Health Sciences|isbn=978-1437727029|page=1502|url=https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}} 3. ^{{cite journal|last=Chilukuri|first=S|author2=Rosen, T|title=Management of acyclovir-resistant herpes simplex virus.|journal=Dermatologic Clinics|date=Apr 2003|volume=21|issue=2|pages=311–20|doi=10.1016/S0733-8635(02)00093-1|pmid=12757254}} 4. ^{{cite journal |vauthors=Segarra-Newnham M, Vodolo KM |title=Use of cidofovir in progressive multifocal leukoencephalopathy |journal=Ann Pharmacother |volume=35 |issue=6 |pages=741–4 |date=June 2001 |pmid=11408993 |doi= 10.1345/aph.10338|url=http://www.theannals.com/cgi/pmidlookup?view=long&pmid=11408993}} 5. ^{{Cite journal | pmid = 23737811| pmc = 3659475| year = 2013| author1 = De Gascun| first1 = C. F.| title = Human polyomavirus reactivation: Disease pathogenesis and treatment approaches| journal = Clinical and Developmental Immunology| volume = 2013| pages = 1–27| last2 = Carr| first2 = M. J.| doi = 10.1155/2013/373579}} 6. ^{{cite journal |author=De Clercq E |title=Cidofovir in the treatment of poxvirus infections|journal=Antiviral Res. |volume=55 |issue=1 |pages=1–13 |date=July 2002 |pmid=12076747 |doi= 10.1016/S0166-3542(02)00008-6|url=http://linkinghub.elsevier.com/retrieve/pii/S0166354202000086}} 7. ^{{cite journal|last=Bradbury|first=J|title=Orally available cidofovir derivative active against smallpox.|journal=Lancet|date=March 2002|volume=359|issue=9311|pages=1041|doi=10.1016/S0140-6736(02)08115-1|pmid=11937193}} 8. ^{{cite journal|last=Magee|first=WC|author2=Hostetler, KY |author3=Evans, DH |title=Mechanism of Inhibition of Vaccinia Virus DNA Polymerase by Cidofovir Diphosphate|journal=Antimicrobial Agents and Chemotherapy|date=August 2005|volume=49|issue=8|pages=3153–3162|doi=10.1128/AAC.49.8.3153-3162.2005|pmid=16048917|pmc=1196213}} 9. ^{{cite journal |vauthors=Araya CE, Lew JF, Fennell RS, Neiberger RE, Dharnidharka VR |title=Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy |journal=Pediatr Transplant |volume=10 |issue=1 |pages=32–7 |date=February 2006|pmid=16499584 |doi=10.1111/j.1399-3046.2005.00391.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1397-3142&date=2006&volume=10&issue=1&spage=32|archive-url=https://archive.today/20130105093701/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1397-3142&date=2006&volume=10&issue=1&spage=32|dead-url=yes|archive-date=2013-01-05}} 10. ^{{cite journal |vauthors=Broekema FI, Dikkers FG |title=Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis |journal=Eur Arch Otorhinolaryngol |volume=265 |issue=8 |pages=871–9 |date=August 2008 |pmid=18458927|pmc=2441494 |doi=10.1007/s00405-008-0658-0}} 11. ^{{cite journal |vauthors=Soma MA, Albert DM |title=Cidofovir: to use or not to use? |journal=Curr Opin Otolaryngol Head Neck Surg |volume=16 |issue=1 |pages=86–90 |date=February 2008 |pmid=18197029|doi=10.1097/MOO.0b013e3282f43408|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00020840-200802000-00019}} 12. ^{{cite web|title=Cidofovir Monograph for Professionals - Drugs.com|work=Drugs.com|publisher=American Society of Health-System Pharmacists|accessdate=5 February 2014|url=https://www.drugs.com/monograph/cidofovir.html}} 13. ^{{cite web|title=Vistide : EPAR -Product Information|work=European Medicines Agency|publisher=Gilead Sciences International Ltd.|date=7 November 2013|accessdate=5 February 2014|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000121/WC500052072.pdf}} 14. ^{{cite journal|last=Fernández-Morano|first=T|author2=del Boz J|author3=González-Carrascosa M|title=Topical cidofovir for viral warts in children|journal=J Eur Acad Dermatol Venereol.|date=2011|volume=25|issue=12|pages=1487–9|doi=10.1111/j.1468-3083.2010.03961.x|pmid=21261749}} 15. ^{{cite journal |vauthors=Liekens S, Gijsbers S, Vanstreels E, Daelemans D, De Clercq E, Hatse S |title=The nucleotide analog cidofovir suppresses basic fibroblast growth factor (FGF2) expression and signaling and induces apoptosis in FGF2-overexpressing endothelial cells |journal=Mol. Pharmacol.|volume=71|issue=3 |pages=695–703 |date=March 2007 |pmid=17158200|doi=10.1124/mol.106.026559|url=http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17158200}} 16. ^{{cite journal|author=Liekens S |title=Regulation of cancer progression by inhibition of angiogenesis and induction of apoptosis|journal=Verh. K. Acad. Geneeskd. Belg. |volume=70 |issue=3 |pages=175–91 |year=2008 |pmid=18669159 |doi= |url=}} 17. ^1 http://www.gilead.com/~/media/Files/pdfs/medicines/other/vistide/vistide.pdf 18. ^Lacy, S. "Effect of Oral Probenecid Coadministration on the Chronic Toxicity and Pharmacokinetics of Intravenous Cidofovir in Cynomolgus Monkeys. 19. ^1 2 {{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }} 20. ^1 2 3 4 {{cite web|title=Vistide (cidofovir) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|accessdate=4 February 2014|url=http://reference.medscape.com/drug/vistide-cidofovir-342606#showall}} 21. ^{{cite web |title= Vistide (cidofovir) |url=http://www.gilead.com/~/media/Files/pdfs/medicines/other/vistide/vistide.pdf |type= package insert |date=September 2010 |publisher=Gilead Sciences |pages= DOSAGE AND ADMINISTRATION: Dosage |nopp= yes}} 22. ^1 2 3 4 5 6 7 {{cite web|title=Product Information VISTIDE®|work=TGA eBusiness Services|publisher=Gilead Sciences Pty Ltd|date=3 September 2013|accessdate=5 February 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-01028-3}} 23. ^{{cite journal|last=Safrin|first=S|author2=Cherrington, J |author3=Jaffe, HS |title=Clinical uses of cidofovir|journal=Reviews in Medical Virology|date=September 1997|volume=7|issue=3|pages=145–156|doi=10.1002/(SICI)1099-1654(199709)7:3<145::AID-RMV196>3.0.CO;2-0|pmid=10398479}} 24. ^{{cite web |url=http://www.gilead.com/pr_881577 |title=Press Releases: Gilead|accessdate=2007-12-05 |format= |website=}} 25. ^{{Cite journal|doi=10.1016/S0040-4039(00)76875-4|title=A practical synthesis of (S)-HPMPC|year=1994|last1=Brodfuehrer|first1=P|journal=Tetrahedron Letters|volume=35|pages=3243|last2=Howell|first2=Henry G.|last3=Sapino|first3=Chester|last4=Vemishetti|first4=Purushotham|issue=20}} 7 : Gilead Sciences|Anti-herpes virus drugs|Pyrimidones|Amines|Ethers|Phosphonic acids|Alcohols |
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