Levetiracetam

KEPPRA · LEVETIRACETAM USP · LEVITIRACETAM · (2R)-2-(2-oxopyrrolidin-1-yl)butanaMide · MFCD00 · SIB-S1 · UCB-L059 · 103833-73-4

https://huagongshe.com/ko/chemical/5284583

식별자 및 물리적 특성

CAS No.	102767-28-2
분자식	C8H14N2O2
평균 분자량	170.21 g/mol
단동위원소 질량	170.10552769 g/mol
SMILES	CC[C@@H](C(N)=O)N1CCCC1=O
InChIKey	HPHUVLMMVZITSG-LURJTMIESA-N
PubChem CID	5284583
ChEMBL	CHEMBL1286
ChEBI	CHEBI:6437
EC No.	600-348-9
DTXSID	DTXSID9023207

화학 및 물리적 성질

XLogP	-0.3
극성 표면적	63.4
수소 결합 공여자 수	1
수소 결합 수용자 수	2
회전 가능 결합 수	3
무거운 원자 수	12
형식 전하	0
복잡도	203
의약품	Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antiepileptic
냄새	Faint
맛	Bitter
Color/Form	Crystals from ethyl acetateWhite to off-white crystalline powder
용해도	104g/100mLVery soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/mL), soluble in ethanol (16.5 g/mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in n-hexane. (Solubility limits are expressed as g/100 mL solvent)H2O: >5mg/mL
Human Drugs	Breast FeedingLactationMilk, HumanAnticonvulsantsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
녹는점	115-119C117 °C118-119°C
증기압	3.5X10-6 mm Hg at 25 °C
Optical Rotation	Specific optical rotation: -90 deg at 25 °C/D (c = 1 in acetone)
인화점	9℃
저장 조건	2-8°C
물리적 상태	가루
색상	하얀색
BCS Class	3
안정성	제공된 대로 구매일로부터 1년 동안 안정적입니다. DMSO의 솔루션은 최대 1개월 동안 -20°에서 보관할 수 있습니다.
주요 응용	임상 시험
InChI	InChI=1/C8H14N2O2/c1-2-6(8(9)12)10-5-3-4-7(10)11/h6H,2-5H2,1H3,(H2,9,12)/t6-/s3
InChIKey	HPHUVLMMVZITSG-UHFFFAOYSA-N
SMILES	C(N)(=O)[C@@H](N1CCCC1=O)CC \|&1:3,r\|

화학적 성질

White Crystalline Solid

안전 및 규제

GHS 분류	This chemical does not meet GHS hazard criteria for 1.7% (2 of 119) of reports.WarningH302 (89.1%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P330, P337+P317, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 119 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
FDA 요건	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levetiracetam, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Hazard Classes and Categories	Acute Tox. 4 (89.1%)
보관 조건	Store at 25 °C (77 °F)excursions permitted to 15-30 °C (59-86 °F)
처리 방법	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Treatment	There is no specific antidote for overdose with Levetiracetam. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavageusual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient's clinical status.
상호 작용	No interaction between probenecid and levetiracetam was observedhowever, probenecid decreased the renal clearance of ucb L057 (inactive metabolite of levetiracetam) by 60%./Levetiracetam/ had no effect on the pharmacokinetic disposition of phenytoin in patients with refractory epilepsy. Pharmacokinetics of levetiracetam were also not affected by phenytoin.Levetiracetam did not alter the pharmacokinetics of valproate in healthy volunteers. Valproate 500 mg twice daily did not modify the rate or extent of levetiracetam absorption or its plasma clearance or urinary excretion. There also was no effect on exposure to and the excretion of the primary metabolite, ucb L057. Potential drug interactions between /levetiracetam/ and other Antiepileptic Drugs (AEDs) (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies. These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam.

용도

개요

Levetiracetam was first introduced in the US as an adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy. This second-generation analog of piracetam can be prepared by condensation of (S)-2-aminobutyramide with 4-chlorobutyryl chloride. Although its mechanism of action is not well established, it was shown that [3H]-levetiracetam reversibly binds to a specific site predominantly present in the membranes of the brain. Unlike conventional anticonvulsants such as phenytoin, carbamazepine, valproic acid, phenobarbital, diazepam and clonazepam, compounds structurally-related to levetiracetam, such as piracetam and aniracetam, also have affinity for this site. Levetiracetam reveals a broad and unique profile in animal seizure models, including promising antiepileptogenic properties. Besides being rapidly and almost completely absorbed in man (oral bioavailability>95%), it possesses a favorable pharmacokinetic profile since it is not hepatically metabolized but only partly hydrolized into the inactive carboxylic acid by enzymes in a number of tissues including blood cells, it is minimally bound to plasma proteins (

역사

Levetiracetam was originally discovered by UCB and is now marketed as Keppra® in over 90 countries worldwide. It was discovered in 1992 through screening in audiogenic seizure susceptible mice. It is available as regular and extended release oral formulations and as intravenous formulations. The immediate release tablet has been available as a generic in the United States since 2008, and in the UK since 2011. The patent for the extended release tablet will expire in 2028. In 2015, Aprecia's orally disintegrating tablet form of the drug manufactured using pharmaceutical 3D printing techniques was approved by the FDA, under the trade name Spritam.

용도

The (S)-enantiomer of the ethyl analog of Piracetam. Used as an anticonvulsant.

일반 설명

LEV is an analog of the nootropic agent, piracetam. Onlythe S-isomer has any anticonvulsant activity. Unlike piracetam, LEV does not have any affinity for the AMPA receptor thereby has no nootropic activity forthe treatment of Alzheimer disease. LEV also has no affinityfor GABA receptors, BZD receptors, the various excitatoryamino acid related receptors, or the voltage-gated ionchannels.For this reason, its mechanism of anticonvulsantaction remains unclear, but it appears to exert itsantiepileptic action by modulating kainite/AMPA-inducedexcitatory synaptic currents, thus decreasing membraneconductance.Furthermore, the anticonvulsant activity ofthis drug appears to be mediated by the parent moleculerather than by its inactive metabolite,(S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid (i.e., via the hydrolysis of amidegroup).Like gabapentin, LEV has few drug interactionswith other AEDs thereby can be used in combination to treatrefractory epilepsy.