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药品详细

Carglumic Acid(卡谷氨酸)

化学结构式图
中文名
卡谷氨酸
英文名
Carglumic Acid
分子式
C6H10N2O5
化学名
(2S)-2-(carbamoylamino)pentanedioic acid
分子量
Average: 190.154
Monoisotopic: 190.05897144
CAS号
1188-38-1
ATC分类
A16A Other Alimentary Tract and Metabolism Products
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Carglumic acid is an orphan drug used for the treatment of hyperammonaemia in patients with N-acetylglutamate synthase deficiency. This rare genetic disorder results in elevated blood levels of ammonia, which can eventually cross the blood–brain barrier and cause neurologic problems, cerebral edema, coma, and death. Carglumic acid was approved by the U.S. Food and Drug Administration (FDA) on 18 March 2010.

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C: N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9. Pubmed
    2. Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M: Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4. Pubmed
    3. Summary of the European Public Assessment Report (EPAR) from European Medicines Agency. Last updated on 21/09/2009. Carbaglu
    4. Thompson CA: Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1;67(9):690. Pubmed
    5. Haberle J: Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency. Ther Clin Risk Manag. 2011;7:327-32. doi: 10.2147/TCRM.S12703. Epub 2011 Aug 2. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication For the treatment of acute and chronic hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency. This enzyme is an important component of the urea cycle to prevent build up of neurotoxic ammonium in the blood.
    Pharmacodynamics The median Tmax of Carbaglu was 3 hours (range: 2-4). The initial daily dose ranges from 100 to 250 mg/kg, adjusted thereafter to maintain normal plasma levels of ammonia.
    Mechanism of action Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG), which is an essential allosteric activator of the liver enzyme carbamoyl phosphate synthetase 1 (CPS1). CPS1 is found in the mitochondria and is the first enzyme of the urea cycle, which converts ammonia into urea. Carglumic acid acts as a replacement for NAG in NAGS deficiency patients by activating CPS1 but it does not help to regulate the urea cycle.
    Absorption 30% bioavailability; Cmax, mean, 100 mg/kg dose = 2.6 μg/mL (range of 1.9 - 4.8) Carglumic acid is not subject to to intracellular degradation.
    Volume of distribution

    The apparent volume of distribution was 2657 L (range: 1616-5797).
    Protein binding Not Available
    Metabolism
    A proportion of carglumic acid may be metabolized by the intestinal bacterial flora. The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs.
    Route of elimination Following administration of a single radiolabeled oral dose of 100 mg/kg of body weight, 9% of the dose was excreted unchanged in the urine and up to 60% of the dose was excreted unchanged in the feces.
    Half life Median values for the terminal half-life was 5.6 hours (range 4.3-9.5).
    Clearance

    The apparent total clearance was 5.7 L/min (range 3.0-9.7), the renal clearance was 290 mL/min (range 204-445), and the 24-hour urinary excretion was 4.5 % of the dose (range 3.5-7.5).
    Toxicity LD50, oral, mouse: >1000 mg/kg
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    logP -1.097 MSDS
    Predicted Properties
    Property Value Source
    water solubility 1.91e+01 g/l ALOGPS
    logP -1.1 ALOGPS
    logP -1.4 ChemAxon
    logS -1 ALOGPS
    pKa (strongest acidic) 3.36 ChemAxon
    pKa (strongest basic) -2.3 ChemAxon
    physiological charge -2 ChemAxon
    hydrogen acceptor count 5 ChemAxon
    hydrogen donor count 4 ChemAxon
    polar surface area 129.72 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 39.41 ChemAxon
    polarizability 16.78 ChemAxon
    药物相互作用
    食物相互作用
    Not Available

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