| 词条 | Brivaracetam |
| 释义 |
| IUPAC_name = (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide | image = Brivaracetam.svg | width = 130 | pronounce = {{IPAc-en|ˌ|b|r|ɪ|v|ə|ˈ|r|æ|s|ə|t|əm}} {{respell|BRIV|ə|RASS|ə-təm}} | tradename = Briviact | Drugs.com = {{Drugs.com|parent|Briviact}} | MedlinePlus = | pregnancy_AU = | pregnancy_AU_comment = | pregnancy_US = C | pregnancy_category = | routes_of_administration = Oral (tablets, oral solution), IV | licence_EU = yes | legal_AU = | legal_AU_comment = | legal_CA = | legal_DE = | legal_NZ = | legal_UK = | legal_US = Schedule V | legal_UN = | legal_status = Rx-only | bioavailability = Nearly 100% | protein_bound = ≤20% | metabolism = Hydrolysis by amidase, CYP2C19-mediated hydroxylation | metabolites = 3 inactive metabolites | onset = | elimination_half-life = ≈9 hours | duration_of_action = | excretion = Kidneys (>95%)[1] | CAS_number = 357336-20-0 | CAS_number_Ref = {{cascite|correct|chemspider}} | ATCvet = | ATC_prefix = N03 | ATC_suffix = AX23 | PubChem = 9837243 | DrugBank = | ChEMBL = 607400 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChemSpiderID = 8012964 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 133013 | UNII = U863JGG2IA | UNII_Ref = {{fdacite|correct|FDA}} | KEGG = D08879 | chemical_formula = | C=11 | H=20 | N=2 | O=2 | molecular_weight = 212.15 g/mol | specific_rotation = [α]D −60° | smiles = O=C(N)[C@@H](N1C(=O)C[C@@H](CCC)C1)CC | StdInChI = 1S/C11H20N2O2/c1-3-5-8-6-10(14)13(7-8)9(4-2)11(12)15/h8-9H,3-7H2,1-2H3,(H2,12,15)/t8-,9+/m1/s1 | StdInChIKey = MSYKRHVOOPPJKU-BDAKNGLRSA-N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | melting_point = 72 | melting_high = 77 }} Brivaracetam (trade name Briviact), a chemical analog of levetiracetam, is a racetam derivative with anticonvulsant (antiepileptic) properties.[2][3] It is marketed by the pharmaceutical company UCB. In India it is co-promoted and distributed by Dr. Reddy's Laboratories. Medical usesBrivaracetam is used to treat partial-onset seizures with or without secondary generalisation, in combination with other antiepileptic drugs. No data are available for its effectiveness and safety in patients younger than 16 years.[4][5] Adverse effectsThe most common adverse effects include sleepiness, dizziness, nausea and vomiting. More rarely, coordination problems and changes in behaviour can occur.[4][5] InteractionsCoadministration of brivaracetam with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine, and could theoretically lead to reduced tolerability. Coadministration of brivaracetam with phenytoin may increase phenytoin levels. Coadministration of other antiseizure drugs are unlikely to affect brivaracetam exposure. Brivaracetam provides no added therapeutic benefit when administered in conjunction with levetiracetam that acts on the same protein.[5] PharmacologyMechanism of actionBrivaracetam is believed to act by binding to the ubiquitous synaptic vesicle glycoprotein 2A (SV2A), like levetiracetam. but with 20-fold greater affinity.[6][7] There is some evidence that racetams including levetiracetam and brivaracetam access the luminal side of recycling synaptic vesicles during vesicular endocytosis. They may reduce excitatory neurotransmitter release and enhance synaptic depression during trains of high-frequency activity, such as is believed to occur during epileptic activity. [8]PharmacokineticsBrivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of 7 to 8 hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the acetamide group, and secondarily through hydroxylation mediated by the liver enzyme CYP2C19. The three major metabolites (hydroxy, acid, and hydroxyacid) are pharmacologically inactive. Brivaracetam is eliminated as urinary metabolites, with over 95% of a radioactive test dose recovered in the urine within 72 hours, including only 8.6% as unchanged brivaracetam.[9] PharmacogeneticsAs noted above, brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, “CYP2C19 poor metabolizers”, will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea.[10] The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction.[11] Chemical and physical propertiesBrivaracetam is the 4R-propyl analogue of the anticonvulsant levetiracetam. {{clear left}}HistoryPositive preliminary results from stage III trials were recorded in 2008,[12] along with evidence that it is around 10 times more potent for the prevention of certain types of seizure in mouse models than its analogue levetiracetam.[13] On 14 January 2016, the European Commission,[14] and on May 12, 2016, the Food and Drug Administration[15] approved brivaracetam under the trade name Briviact. The Drug Enforcement Administration (DEA) has issued an interim final rule{{clarify|date=May 2016|reason=What is "interim final"? Seems contradictory.}} placing brivaracetam into schedule V of the Controlled Substances Act (CSA) effective Mar 09, 2017.[16] {{as of|2016|5}}, brivaracetam is not approved in other countries, including Australia, Canada and Switzerland. References1. ^{{cite web|title=Briviact (brivaracetam) Tablets, for Oral Use; Oral Solution; Injection, for Intravenous Use. CV. Full Prescribing Information|url=https://www.briviact.com/briviact-PI.pdf|publisher=UCB, Inc., Smyrna, GA 30080|accessdate=27 August 2016}} 2. ^{{cite journal | vauthors = von Rosenstiel P | title = Brivaracetam (UCB 34714) | journal = Neurotherapeutics | volume = 4 | issue = 1 | pages = 84–7 | date = Jan 2007 | pmid = 17199019 | doi = 10.1016/j.nurt.2006.11.004 }} 3. ^{{cite journal | vauthors = Malawska B, Kulig K | title = Brivaracetam UCB | journal = Current Opinion in Investigational Drugs | volume = 6 | issue = 7 | pages = 740–746 | date = Jul 2005 | pmid = 16044671 }} 4. ^1 Drugs.com: {{Drugs.com|parent|briviact}} for Briviact. 5. ^{{cite journal |vauthors= Rolan P, Sargentini-Maier ML, Pigeolet E, Stockis A |date= 2008|title= The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men |journal= Br J Clin Pharmacol|volume=66 |issue=1 |pages=71–5 |pmc= 2485265|pmid=18341673 |doi= 10.1111/j.1365-2125.2008.03158.x}} 6. ^{{cite journal | vauthors = Rogawski MA, Bazil CW | title = New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels | journal = Current Neurology and Neuroscience Reports | volume = 8 | issue = 4 | pages = 345–352 | date = Jul 2008 | pmid = 18590620 | pmc = 2587091 | doi = 10.1007/s11910-008-0053-7 }} 7. ^{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}} 8. ^{{cite journal | author = Rogawski MA | date=2016 | title=A new SV2A ligand for epilepsy | journal=Cell | volume=167| pages=587|doi= 10.1016/j.cell.2016.09.057 | pmid=27768878}} 9. ^{{cite journal |vauthors= Sargentini-Maier ML, Espié P, Coquette A, Stockis A |date= 2008 |title= Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects|journal= Drug Metab. Dispos. |volume= 36|issue=1 |pages=36–45 |pmid= 17908923|doi= 10.1124/dmd.107.017129 }} 10. ^{{Citation|last=Dean|first=Laura|title=Brivaracetam Therapy and CYP2C19 Genotype|date=2012|url=https://www.ncbi.nlm.nih.gov/books/NBK500036/|work=Medical Genetics Summaries|editor-last=Pratt|editor-first=Victoria|publisher=National Center for Biotechnology Information (US)|pmid=29763212|access-date=2019-01-25|editor2-last=McLeod|editor2-first=Howard|editor3-last=Rubinstein|editor3-first=Wendy|editor4-last=Dean|editor4-first=Laura}} 11. ^{{Cite web|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3cf2f439-0e97-443e-8e33-25ecef616f6c|title=DailyMed - BRIVIACT- brivaracetam tablet, film coated BRIVIACT- brivaracetam solution BRIVIACT- brivaracetam injection, suspension|website=dailymed.nlm.nih.gov|access-date=2019-01-25}} 12. ^{{cite journal | vauthors = Rogawski MA | title = Brivaracetam: a rational drug discovery success story | journal = British Journal of Pharmacology | volume = 154 | issue = 8 | pages = 1555–7 | date = Aug 2008 | pmid = 18552880 | pmc = 2518467 | doi = 10.1038/bjp.2008.221 }} 13. ^{{cite journal | vauthors = Matagne A, Margineanu DG, Kenda B, Michel P, Klitgaard H | title = Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A | journal = British Journal of Pharmacology | volume = 154 | issue = 8 | pages = 1662–71 | date = Aug 2008 | pmid = 18500360 | pmc = 2518465 | doi = 10.1038/bjp.2008.198 }} 14. ^1 2 {{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003898/human_med_001945.jsp&mid=WC0b01ac058001d124|title=Briviact|publisher=European Medicines Agency|access-date=30 May 2016}} 15. ^{{cite news|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486827.htm|title=FDA approves Briviact to treat partial onset seizures|publisher=US FDA|date=May 12, 2016}} 16. ^{{ cite journal | author = Drug Enforcement Administration Department of Justice | title = Schedules of Controlled Substances: Placement of Brivaracetam Into Schedule V. Interim final rule, with request for comments. | journal = Fed Regist |date = Nov 25, 2015 | volume = 81 | issue = 92 | pages = 29487–92 | pmid = 27192732 }} External links
3 : Racetams|Carboxamides|Anticonvulsants |
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