Aripiprazole Lauroxil
(Synonyms: 月桂酰阿立派唑) 目录号 : GC60598
Aripiprazolelauroxil，阿立哌唑的N-酰氧基甲基前药形式，一种长效注射剂(LAI)的抗精神病药物。Aripiprazolelauroxil被体内酯酶裂解为N-羟甲基阿立哌唑(月桂酸)，再裂解为阿立哌唑，无毒。
Cas No.:1259305-29-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Aripiprazole lauroxil, an N-acyloxymethyl prodrug of aripiprazole, is a Long-acting injectable (LAI) typical antipsychotic for schizophrenia. Aripiprazole lauroxil is cleaved by body's enzyme esterase to N-hydroxymethyl aripiprazole (plus lauric acid) and then to aripiprazole (plus formaldehyde), no toxicity[1].
Aripiprazole lauroxil (intravenous administration; 1.87 mg/ml) bioconversion in vivo involves the formation of an intermediate, N-hydroxymethyl aripiprazole, the in vitro data indicates a high bioconversion of aripiprazole lauroxil, thus, the concentration of N-hydroxymethyl aripiprazole observed in the animals dosed with aripiprazole lauroxil is surprisingly high[1]. Animal Model: Female Sprague Dawley rats[1]
[1]. Jann MW, et al. Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents.CNS Drugs. 2018 Mar;32(3):241-257. [2]. Rohde M, et al. Biological conversion of aripiprazole lauroxil - An N-acyloxymethyl aripiprazole prodrug.Results Pharma Sci. 2014 May 2;4:19-25.
| Cas No. | 1259305-29-7 | SDF | |
| 别名 | 月桂酰阿立派唑 | ||
| Canonical SMILES | CCCCCCCCCCCC(OCN1C(CCC2=C1C=C(OCCCCN3CCN(C4=CC=CC(Cl)=C4Cl)CC3)C=C2)=O)=O | ||
| 分子式 | C36H51Cl2N3O4 | 分子量 | 660.71 |
| 溶解度 | DMSO: 8.33 mg/mL (12.61 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5135 mL | 7.5676 mL | 15.1352 mL |
| 5 mM | 0.3027 mL | 1.5135 mL | 3.027 mL |
| 10 mM | 0.1514 mL | 0.7568 mL | 1.5135 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Aripiprazole Lauroxil Dosing Regimens: Understanding Dosage Strengths and Injection Intervals
CNS Spectr 2022 Jun;27(3):262-267.PMID:33267924DOI:10.1017/S1092852920002072.
Aripiprazole Lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three different injection intervals using four different dosage strengths. The relationship between dosage strength (milligram injected), injection interval (time between injection visits), and expected steady-state plasma aripiprazole concentrations may not be readily apparent. This article illustrates the relationship by providing visual scenarios of steady-state plasma aripiprazole concentrations for the five AL regimens. The efficacy of AL was originally demonstrated in a pivotal study of two AL regimens (approved as 441 mg monthly and 882 mg monthly). The three additional regimens (662 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months) were approved based on pharmacokinetic bridging studies and population pharmacokinetic models. For this paper, expected steady-state concentrations for each AL regimen were derived from the published population pharmacokinetic models and compared using median values and ranges. The five labeled AL regimens differ in dosage strength and injection interval; however, model-simulated concentrations illustrate that each regimen produces steady-state plasma aripiprazole concentrations within the upper and lower bounds associated with known efficacy for AL 441 mg and 882 mg administered monthly. This visual presentation of the relationship between dosage strength of the AL injection, the interval between successive injections, and steady-state aripiprazole plasma concentrations may demonstrate for clinicians how dosage strength and injection interval can be considered in selecting the AL regimen option that best fits the clinical circumstances of the individual patient.
A safety evaluation of aripiprazole in the treatment of schizophrenia
Expert Opin Drug Saf 2020 Dec;19(12):1529-1538.PMID:33064050DOI:10.1080/14740338.2020.1832990.
Introduction: Aripiprazole is a third generation antipsychotic approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Aripiprazole is available as oral and long-acting injectable (LAI) depot formulations, with a unique mechanism of action comprising partial D2 and serotonin 5-HT1A agonism and antagonism at serotonin 5-HT2A receptors. Areas covered: We review short-and-long-term clinical trials, meta-analyses of clinical trials and product information pertaining to the safety and efficacy of aripiprazole in adults with schizophrenia. Formulations of aripiprazole reviewed include oral aripiprazole, Aripiprazole monohydrate LAI (Abilify Maintena©) and Aripiprazole Lauroxil LAI (Aristada©). Clinical studies and product information were collected from PubMed, Psychinfo, Embase, and other web sources. Expert opinion: Aripiprazole is a generally well-tolerated third-generation antipsychotic with low rates of motor side effects and metabolic adverse effects that occur commonly with several alternative antipsychotics. Akathisia and tremor appear to occur at higher rates with aripiprazole compared to placebo but are still generally uncommon with incidences of 10-11% or less. Uniquely, aripiprazole treatment is associated with reduced serum prolactin levels and QTc interval. A variety of LAI options with dosing intervals as infrequent as every 8 weeks provide a compelling reason to select aripiprazole in patients with limited oral treatment adherence.
Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review
Neurol Int 2021 Jul 1;13(3):279-296.PMID:34287335DOI:10.3390/neurolint13030029.
Purpose of review: This is a comprehensive review of the literature regarding the use of Aripiprazole Lauroxil for schizophrenia. This review presents the background, evidence, and indications for using Aripiprazole Lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent findings: Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole Lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole Lauroxil was FDA approved in October of 2015. Summary: Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, Aripiprazole Lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole Lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective.
Aripiprazole Lauroxil: A Review in Schizophrenia
Drugs 2017 Dec;77(18):2049-2056.PMID:29177572DOI:10.1007/s40265-017-0848-4.
Aripiprazole Lauroxil long-acting injectable (LAI) [Aristada®] is an intramuscularly administered, extended-release prodrug of aripiprazole, an established atypical antipsychotic agent that, in terms of its relative position within the class, is at the low end of the risk spectrum for metabolic side effects. In the USA, Aripiprazole Lauroxil LAI is indicated for the treatment of schizophrenia; approved doses of the drug can be injected once-monthly (q4w), every 6 weeks (q6w) or every 2 months (q8w). The efficacy of the 441 and 882 mg q4w dosages in the treatment of acute exacerbations of schizophrenia and as long-term maintenance therapy in stable schizophrenia has been directly demonstrated in a phase III clinical trial and extension, while the efficacy of the 662 mg q4w, 882 mg q6w and 1064 mg q8w dosing regimens has been established on the basis of pharmacokinetic bridging studies. Aripiprazole Lauroxil LAI therapy was generally well tolerated, with an adverse event profile consistent with that of oral aripiprazole (with the exception of injection-site reactions), including a low propensity to cause metabolic disturbances. Thus, Aripiprazole Lauroxil LAI extends the treatment regimen options for patients with schizophrenia; as with other LAI formulations of antipsychotic agents, it can be particularly recommended for patients with recurrent relapses related to nonadherence to oral preparations and for those who prefer this mode of administration. Moreover, unlike aripiprazole monohydrate LAI, the only other commercially available long-acting formulation of aripiprazole, Aripiprazole Lauroxil LAI offers more than one dosing interval option, which may be a potential advantage in terms of tailoring therapy to the needs of individual patients.
New Antipsychotic Medications in the Last Decade
Curr Psychiatry Rep 2021 Nov 29;23(12):87.PMID:34843030DOI:10.1007/s11920-021-01298-w.
Purpose of review: Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current review summarizes these developments over the past decade (2011-2020). We performed a systematic review utilizing PubMed and PsychInfo with the aim of identifying all the RCT and related analyses in adults with psychosis (schizophrenia and mania). Recent findings: We identified 11 significant developments: the introduction of new antipsychotics cariprazine, brexpiprazole, lumateperone, and pimavanserin; introduction of new delivery methods: subcutaneous long-acting risperidone, Aripiprazole Lauroxil, transdermal asenapine, and inhaled loxapine; and the introduction of new approaches such as olanzapine/samidorphan for olanzapine-associated weight gain, examination of the TAAR1 agonist SEP 363,856 as a test of concept, and the combination of Xanomeline/Trospium, an M1 and M4 muscarinic receptor agonist in conjunction with a peripheral anticholinergic. Last decade has seen a tremendous development in second-generation antipsychotics which provides unprecedented treatment options for clinicians in treating psychosis.