Details of the Drug

General Information of Drug (ID: DMSEPK8)

Drug Name

Brivaracetam

Synonyms

Rikelta; UCB-34714; Brivaracetam (USAN/INN)

Indication

Disease Entry	ICD 11	Status	REF
Complex partial seizure	8A68.0	Approved	[1]
Epilepsy	8A60-8A68	Phase 3	[2], [3]
Pain	MG30-MG3Z	Phase 3	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

212.29

Topological Polar Surface Area (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Bioavailability: The bioavailability of drug is 100% [4]
Clearance: The clearance of drug is 0.7-1.07 mL/min/kg [5]
Elimination: More than 95% of excreted in urine with less than 10% of the parent compound unchanged, and less than 1% excreted in feces [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 7 - 8 hours [4]
Metabolism: The drug is metabolized via the hydrolysis of the acetamide moeity to form a carboxylic acid metabolite [7]
Unbound Fraction: The unbound fraction of drug in plasma is 0.825% [8]
Vd: The volume of distribution (Vd) of drug is 0.5 L/kg [6]

Chemical Identifiers

Formula: C11H20N2O2
IUPAC Name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide
Canonical SMILES: CCC[C@@H]1CC(=O)N(C1)[C@@H](CC)C(=O)N
InChI: InChI=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
InChIKey: MSYKRHVOOPPJKU-BDAKNGLRSA-N

Cross-matching ID

PubChem CID: 9837243
ChEBI ID: CHEBI:133013
CAS Number: 357336-20-0
DrugBank ID: DB05541
TTD ID: D0CT4D
INTEDE ID: DR0230
ACDINA ID: D00078

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Synaptic vesicle glycoprotein 2A (SV2A)	TTT3P91	SV2A_HUMAN	Inhibitor	[9], [10]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[11]
Mephenytoin 4-hydroxylase (CYP2C19)_{Main DME}	DEGTFWK	CP2CJ_HUMAN	Substrate	[12]
Cytochrome P450 2B6 (CYP2B6)_{Main DME}	DEPKLMQ	CP2B6_HUMAN	Substrate	[12]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Brivaracetam (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levomilnacipran	DMV26S8	Moderate	Antagonize the effect of Brivaracetam when combined with Levomilnacipran.	Chronic pain [MG30]	[40]
Levonorgestrel	DM1DP7T	Minor	Increased metabolism of Brivaracetam caused by Levonorgestrel mediated induction of CYP450 enzyme.	Contraceptive management [QA21]	[41]
Vilazodone	DM4LECQ	Moderate	Antagonize the effect of Brivaracetam when combined with Vilazodone.	Depression [6A70-6A7Z]	[40]
Vortioxetine	DM6F1PU	Moderate	Antagonize the effect of Brivaracetam when combined with Vortioxetine.	Depression [6A70-6A7Z]	[40]
Desvenlafaxine	DMHD4PE	Moderate	Antagonize the effect of Brivaracetam when combined with Desvenlafaxine.	Depression [6A70-6A7Z]	[40]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Brivaracetam and Esketamine.	Depression [6A70-6A7Z]	[42]
Oestradiol valerate and dienogest	DMZK0FQ	Minor	Increased metabolism of Brivaracetam caused by Oestradiol valerate and dienogest mediated induction of CYP450 enzyme.	Endometriosis [GA10]	[43]
Etravirine	DMGV8QU	Minor	Decreased metabolism of Brivaracetam caused by Etravirine mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[41]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Brivaracetam and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[44]
ABIRATERONE	DM8V75C	Minor	Decreased metabolism of Brivaracetam caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[41]
Armodafinil	DMGB035	Minor	Decreased metabolism of Brivaracetam caused by Armodafinil mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[41]
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⏷ Show the Full List of 11 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Brivaracetam 75 mg tablet	75 mg	Oral Tablet	Oral
Brivaracetam 100 mg tablet	100 mg	Oral Tablet	Oral
Brivaracetam 25 mg tablet	25 mg	Oral Tablet	Oral
Brivaracetam 50 mg tablet	50 mg	Oral Tablet	Oral
Brivaracetam 10 mg tablet	10 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
2	New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Curr Neurol Neurosci Rep. 2008 Jul;8(4):345-52.
3	Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43.
4	The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008 Jul;66(1):71-5. doi: 10.1111/j.1365-2125.2008.03158.x. Epub 2008 Mar 13.
5	Sargentini-Maier ML, Rolan P, Connell J, Tytgat D, Jacobs T, Pigeolet E, Riethuisen JM, Stockis A: The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol. 2007 Jun;63(6):680-8. Epub 2007 Jan 12.
6	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
7	Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP: Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab. 2009 Feb;94(2):545-51. doi: 10.1210/jc.2008-1695. Epub 2008 Nov 25.
8	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9	Pharmacological management of epilepsy: recent advances and future prospects. Drugs. 2008;68(14):1925-39.
10	New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs. 2006 Jun;15(6):637-47.
11	Effect of gemfibrozil on the metabolism of brivaracetam in vitro and in human subjects. Drug Metab Dispos. 2012 Aug;40(8):1466-72.
12	Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos. 2008 Jan;36(1):36-45.
13	Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
14	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
15	Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
16	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
17	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
18	Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
19	New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
20	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
21	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
22	Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
23	Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
24	Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
25	Drugs that may have potential CYP2B6 interactions.
26	Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
27	Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
28	PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
29	Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
30	High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
31	Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
32	CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
33	Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
34	Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
35	Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
36	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
37	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
38	Pharmacological Profile of the Novel Antiepileptic Drug Candidate Padsevonil: Characterization in Rodent Seizure and Epilepsy Models. J Pharmacol Exp Ther. 2020 Jan;372(1):11-20.
39	Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
40	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
41	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
42	Cerner Multum, Inc. "Australian Product Information.".
43	Product Information. Briviact (brivaracetam). UCB Pharma Inc, Smyrna, GA.
44	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.