Dehydroaripiprazole
(Synonyms: 7-[4-[4-(2,3-二氯苯基)-1-哌嗪基]丁氧基]-2(1H)-喹啉酮,OPC-14857; DM-14857) 目录号 : GC39705
Dehydroaripiprazole (OPC-14857) 是 Aripiprazole 的活性代谢产物。Aripiprazole 是一种抗精神病药，被 CYP3A4 和 CYP2D6 代谢，主要形成 Dehydroaripiprazole。Dehydroaripiprazole 具有与 Aripiprazole 同等的抗精神病活性。
Cas No.:129722-25-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dehydroaripiprazole (OPC-14857) is an active metabolite of Aripiprazole. Aripiprazole is an antipsychotic agent and is metabolized by CYP3A4 and CYP2D6 forming mainly Dehydroaripiprazole. Dehydroaripiprazole has with antipsychotic activity equivalent to Aripiprazole[1][2][3].
[1]. Kirschbaum KM, et al. Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects. World J Biol Psychiatry. 2008;9(3):212-8. [2]. Lin SK, et al. Aripiprazole and dehydroaripiprazole plasma concentrations and clinical responses in patients with schizophrenia. J Clin Psychopharmacol. 2011 Dec;31(6):758-62. [3]. Hui-ChingHuang, et al. Detection and quantification of aripiprazole and its metabolite, dehydroaripiprazole, by gas chromatography-mass spectrometry in blood samples of psychiatric patients. Journal of Chromatography B. Volume 856, Issues 1-2, 1 September 2007, Pages 57-61. [4]. Stip E, Tourjman V. et al. Aripiprazole in schizophrenia and schizoaffective disorder: A review. Clin Ther. 2010;32 Suppl 1:S3-20.
| Cas No. | 129722-25-4 | SDF | |
| 别名 | 7-[4-[4-(2,3-二氯苯基)-1-哌嗪基]丁氧基]-2(1H)-喹啉酮,OPC-14857; DM-14857 | ||
| Canonical SMILES | O=C1NC2=C(C=CC(OCCCCN3CCN(C4=CC=CC(Cl)=C4Cl)CC3)=C2)C=C1 | ||
| 分子式 | C23H25Cl2N3O2 | 分子量 | 446.37 |
| 溶解度 | DMSO : 20 mg/mL (44.81 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.2403 mL | 11.2015 mL | 22.4029 mL |
| 5 mM | 0.4481 mL | 2.2403 mL | 4.4806 mL |
| 10 mM | 0.224 mL | 1.1201 mL | 2.2403 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 and Dehydroaripiprazole plasma concentrations and clinical responses in patients with schizophrenia
J Clin Psychopharmacol 2011 Dec;31(6):758-62.PMID:22020350DOI:10.1097/JCP.0b013e3182356255.
Aripiprazole is widely used to treat schizophrenia. Plasma levels of aripiprazole and its active metabolite Dehydroaripiprazole and their clinical responses in patients were explored. Forty-five (male/female: 19/26) patients with schizophrenia were treated with aripiprazole after a washout period of at least 3 days. There was no concomitant psychotropic except benzodiazepines for insomnia. The Positive and Negative Syndrome Scale (PANSS) was used to measure the clinical response at baseline and at weeks 2, 4, and 6. Blood was drawn at week 6 to measure the plasma concentrations of aripiprazole and Dehydroaripiprazole. Patients with a PANSS score that decreased by more than 20% were defined as responders after 6 weeks of treatment. There was no difference in baseline PANSS scores or the daily dosage used between responders (n = 28) and nonresponders (n = 17) (15.0 ± 5.9 vs 12.9 ± 6.9 mg, respectively; P = 0.203). The responders showed a trend toward a higher plasma concentration of aripiprazole than nonresponders (234.4 ± 156.7 vs 163.5 ± 77.2 ng/mL, respectively; P = 0.117) and a significantly higher plasma concentration of Dehydroaripiprazole (101.6 ± 58.0 vs 66.0 ± 48.4, respectively; P = 0.023). Higher plasma concentrations of aripiprazole and its active metabolite Dehydroaripiprazole were noted in responders than nonresponders. Compared with Western patients, Oriental patients had higher plasma concentrations of aripiprazole and Dehydroaripiprazole at the same dose. We suggest that therapeutic drug monitoring of aripiprazole will help improve the response in clinical practice.
Concentrations of aripiprazole and Dehydroaripiprazole in hair segments from deceased individuals with mental disorders
Forensic Sci Int 2020 Dec;317:110523.PMID:33010563DOI:10.1016/j.forsciint.2020.110523.
Segmental hair analysis provides information regarding previous long-term drug exposure, which is useful in the evaluation of cause of death for individuals with mental disorders. The aim was to analyze postmortem concentrations of the antipsychotic drug aripiprazole and its active metabolite Dehydroaripiprazole in hair segments from individuals with known aripiprazole intake. Hair samples were collected during autopsy. Each sample was segmented into one to six 1cm segments, depending on the length of the hair shaft. Pulverized hair was extracted and analyzed using a previously published ultra-high-performance liquid chromatography-tandem mass spectrometric method. The 10th-90th percentile of aripiprazole concentrations in all hair segments (n=78) from 17 individuals were 0.024ng/mg-11ng/mg with a median of 2.3ng/mg, and the 10th-90th percentile concentrations of Dehydroaripiprazole were 0.020ng/mg-11ng/mg, with a median of 2.6ng/mg, in all hair segments (n=71). The metabolite-to-parent drug ratios ranged from 0.21 to 1.5, with a median of 0.72. The administered doses were calculated for each individual based on aripiprazole prescription data and pharmacy pickups, giving dose estimates of 1mg-32mg daily. A positive significant correlation was observed between concentrations in hair and blood, whereas no trends were observed between the concentrations in hair and the estimated doses. Besides aripiprazole, other antipsychotic drugs were found in several hair segments, indicating a high degree of polypharmacy among all subjects. The present study establishes concentrations of aripiprazole and Dehydroaripiprazole in hair segments from 17 deceased individuals with long-term aripiprazole use. In addition, hair analysis demonstrates the possibility of evaluating polypharmacy.
Influence of comedication on serum concentrations of aripiprazole and Dehydroaripiprazole
Ther Drug Monit 2009 Apr;31(2):233-8.PMID:19142178DOI:10.1097/FTD.0b013e3181956726.
Aripiprazole, a relatively new antipsychotic drug, is metabolized by cytochrome P450 3A4 (CYP3A4) and CYP2D6 to an active metabolite, Dehydroaripiprazole. As studies on pharmacokinetic drug interactions with aripiprazole are so far limited, the aim of the present study was to investigate the impact of comedication on serum concentrations of aripiprazole and Dehydroaripiprazole in psychiatric patients in a clinical setting. A therapeutic drug monitoring database was screened for patients receiving aripiprazole tablets as part of their treatment. Of the 361 samples included, 78% were from patients receiving comedication. The remaining 79 samples constituted the control group. Steady-state dose-adjusted serum concentrations (concentration to dose ratios, C:D ratios) of aripiprazole, Dehydroaripiprazole and the sum of aripiprazole and Dehydroaripiprazole, and the metabolic ratio (Dehydroaripiprazole/aripiprazole) in the different comedication groups were compared with controls. Coadministration of a CYP3A4 inducer resulted in approximately 60% lower mean C:D ratios of aripiprazole, Dehydroaripiprazole, and the sum of aripiprazole and Dehydroaripiprazole (P < 0.05, P < 0.01, and P < 0.01, respectively). Combination with a CYP2D6 inhibitor resulted in a 45% higher mean C:D ratio of aripiprazole (P < 0.05), with no effect on the C:D ratio of Dehydroaripiprazole. When aripiprazole was coadministered with alimemazine or lithium, a 56% (P < 0.01) and 43% (P = 0.05) higher mean C:D ratio of aripiprazole, respectively, was observed. Olanzapine, risperidone injections, escitalopram, or lamotrigine also had statistically significant effects on aripiprazole disposition but to a lesser extent. In conclusion, concurrent treatment with CYP3A4 inducers, CYP2D6 inhibitors, alimemazine, or lithium resulted in changes in the systemic exposure of aripiprazole between 40% and 60%. This is of such a magnitude that dose adjustments of aripiprazole may be required.
Large variability of aripiprazole and Dehydroaripiprazole serum concentrations in adolescent patients with schizophrenia
Ther Drug Monit 2008 Aug;30(4):462-6.PMID:18641558DOI:10.1097/FTD.0b013e318178e18d.
Aripiprazole is a fairly new atypical antipsychotic substance. It acts as a partial D2- and 5-HT1A-agonist and as a 5-HT2A-antagonist. To date, there are few data concerning the dose-serum concentration relationship in children and adolescent psychiatric patients. Also, there are only few data on the influence of age, sex, body mass index, smoking behavior, and comedication on aripiprazole serum concentrations. In 33 consecutively admitted patients of a child and adolescent psychiatric hospital [age (mean +/- standard deviation) 18.7 +/- 1.7 years (range, 13.5-21.6 years)], 117 steady-state serum concentrations (repeated samples from individuals) of aripiprazole and its metabolite Dehydroaripiprazole were assessed using high-performance liquid chromatography. The aripiprazole (mean +/- standard deviation) daily dose was 12.9 +/- 6.4 mg (range, 5-30 mg); the aripiprazole serum concentration was 142.0 +/- 122.7 ng/mL (range, 40.0-648.3 ng/mL; interquartile range, 74.0-167.0 ng/mL). The mean Dehydroaripiprazole serum concentration was 51.6 +/- 22.3 ng/mL (range, 30.0-111.6 ng/mL; interquartile range, 34.3-62.1 ng/mL). There was a positive correlation between oral dose and serum concentrations of aripiprazole (r = 0.548, P = 0.001) and Dehydroaripiprazole (r = 0.740, P < 0.0005). Aripiprazole serum concentrations showed high inter- and intraindividual variability. Intraindividual variability was one- to 9.3-fold (Dehydroaripiprazole: one- to 8.6-fold) and maximum interindividual variability 6.4-fold (Dehydroaripiprazole: 6.8-fold). No significant influence was detected for age, sex, body mass index, comedication, and smoking on concentration-to-dose aripiprazole serum concentrations. Further studies are required to obtain data on the relationship between serum concentrations and resulting clinical effects.
Serum levels of aripiprazole and Dehydroaripiprazole, clinical response and side effects
World J Biol Psychiatry 2008;9(3):212-8.PMID:17853280DOI:10.1080/15622970701361255.
Aripiprazole, a novel antipsychotic drug, is metabolized by CYP3A4 and CYP2D6 forming mainly its active metabolite Dehydroaripiprazole. In this study, aripiprazole and Dehydroaripiprazole serum levels of psychiatric patients were measured and related to dose, comedication, and clinical effects including therapeutic and side effects. Patients were treated with mean doses of 20 +/- 8 mg/day of aripiprazole (median 15 mg, range 7.5-60 mg). Serum levels correlated significantly with the dose (r = 0.419; P < 0.01), with a mean value of aripiprazole of 214 +/- 140 ng/ml. Mean concentrations of the active metabolite Dehydroaripiprazole amounted to 40% of the parent compound. Comedication with CYP3A4 and CYP2D6 inducers or inhibitors changed serum levels up to 51%. Improvement was best in patients with a serum level between 150 and 300 ng/ml. No or only mild side effects were detected in patients, with aripiprazole plasma concentrations between 110 and 249 ng/ml. A total of 32% of the patients who received no other antipsychotic drug besides aripiprazole reported side effects; tension being the most frequent one. Since serum levels of aripiprazole and Dehydroaripiprazole were highly variable between individuals, and distinct ranges were associated with good therapeutic response and minimal side effects, it seems likely that therapeutic drug monitoring can be helpful to improve the antipsychotic drug therapy.