Cysteamine bitartrate
(Synonyms: Mercaptamine bitartrate) 目录号 : GC25330Cysteamine bitartrate (Mercaptamine bitartrate) is an FDA-approved cystine-depleting aminothiol agent for the treatment of nephropathic cystinosis to decrease accumulation of lysosomal cystine by engaging in disulfide exchange. In addition, cysteamine bitartrate has antioxidant properties.
Cas No.:27761-19-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- Datasheet
Cysteamine bitartrate (Mercaptamine bitartrate) is an FDA-approved cystine-depleting aminothiol agent for the treatment of nephropathic cystinosis to decrease accumulation of lysosomal cystine by engaging in disulfide exchange. In addition, cysteamine bitartrate has antioxidant properties.
[1] Guha S, et al. Hum Mol Genet. 2019 Jun 1;28(11):1837-1852.
| Cas No. | 27761-19-9 | SDF | Download SDF |
| 别名 | Mercaptamine bitartrate | ||
| 分子式 | C6H13NO6S | 分子量 | 227.24 |
| 溶解度 | DMSO: 45 mg/mL (198.03 mM);Water: 45 mg/mL (198.03 mM);Ethanol: Insoluble | 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 | 4.4006 mL | 22.0032 mL | 44.0063 mL |
| 5 mM | 0.8801 mL | 4.4006 mL | 8.8013 mL |
| 10 mM | 0.4401 mL | 2.2003 mL | 4.4006 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。
A systematic literature review of Cysteamine bitartrate in the treatment of nephropathic cystinosis
Curr Med Res Opin 2017 Nov;33(11):2065-2076.PMID:28692321DOI:10.1080/03007995.2017.1354288.
Objectives: To summarize available clinical evidence for Cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR). Methods: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) Cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR) Cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included. Results: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR Cysteamine bitartrate (n = 267 patients), 42 describe IR Cysteamine bitartrate (n = 1,427 patients) and in 53 studies the exact preparation was not specified (n = 906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n = 49) being the most common study design representing 47% of the total. Conclusion: A substantial evidence base for Cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4.
Pre-clinical evaluation of Cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease
Hum Mol Genet 2019 Jun 1;28(11):1837-1852.PMID:30668749DOI:10.1093/hmg/ddz023.
Cysteamine bitartrate is a US Food and Drug Administration-approved therapy for nephropathic cystinosis also postulated to enhance glutathione biosynthesis. We hypothesized this antioxidant effect may reduce oxidative stress in primary mitochondrial respiratory chain (RC) disease, improving cellular viability and organismal health. Here, we systematically evaluated the therapeutic potential of Cysteamine bitartrate in RC disease models spanning three evolutionarily distinct species. These pre-clinical studies demonstrated the narrow therapeutic window of Cysteamine bitartrate, with toxicity at millimolar levels directly correlating with marked induction of hydrogen peroxide production. Micromolar range Cysteamine bitartrate treatment in Caenorhabditis elegans gas-1(fc21) RC complex I (NDUFS2-/-) disease invertebrate worms significantly improved mitochondrial membrane potential and oxidative stress, with corresponding modest improvement in fecundity but not lifespan. At 10 to 100 μm concentrations, Cysteamine bitartrate improved multiple RC complex disease FBXL4 human fibroblast survival, and protected both complex I (rotenone) and complex IV (azide) Danio rerio vertebrate zebrafish disease models from brain death. Mechanistic profiling of Cysteamine bitartrate effects showed it increases aspartate levels and flux, without increasing total glutathione levels. Transcriptional normalization of broadly dysregulated intermediary metabolic, glutathione, cell defense, DNA, and immune pathways was greater in RC disease human cells than in C. elegans, with similar rescue in both models of downregulated ribosomal and proteasomal pathway expression. Overall, these data suggest Cysteamine bitartrate may hold therapeutic potential in RC disease, although not through obvious modulation of total glutathione levels. Careful consideration is required to determine safe and effective Cysteamine bitartrate concentrations to further evaluate in clinical trials of human subjects with primary mitochondrial RC disease.
Pharmacokinetics of enteric-coated Cysteamine bitartrate in healthy adults: a pilot study
Br J Clin Pharmacol 2010 Sep;70(3):376-82.PMID:20716238DOI:10.1111/j.1365-2125.2010.03721.x.
What is already known about this subject: Cysteamine bitartrate is taken lifelong, every 6 h and for the treatment of cystinosis. Recent studies using cysteamine for for other diseases such as neurodegenerative disorders adopt the same dosing regimen for cysteamine. Regular Cysteamine bitartrate (Cystagon) may cause upper gastrointestinal symptoms in some patients. What this study adds: This is the only study that provides pharmacokinetic data for cysteamine delivered in an enteric-release preparation in normal subjects. EC-cysteamine is very well tolerated and does not cause increased gastrin concentrations, even at relatively high doses. EC-cysteamine at the higher dose results in better drug uptake as measured by Cmax and AUC and is more likely to be effective. Aims: Cysteamine bitartrate (Cystagon) is the approved treatment for cystinosis. Poor compliance and patient outcome may occur because the drug needs to be taken every 6 h and in some patients causes gastrointestinal symptoms due to hypergastrinaemia. A formulation of cysteamine requiring twice daily ingestion would improve the quality of life for these patients. This study compares the pharmacokinetics and gastrin production following Cysteamine bitartrate non-enteric-coated and Cysteamine bitartrate enteric-coated in normal healthy subjects. Methods: Enteric-coated cysteamine was prepared. Following single doses of Cysteamine bitartrate non-enteric-coated 450 mg and Cysteamine bitartrate enteric-coated 450 mg and 900 mg, serial plasma cysteamine and gastrin concentrations were measured. Two subjects also received Cysteamine bitartrate non-enteric-coated 900 mg. Gastrointestinal (GI) symptoms were recorded. Results: Six healthy adults (mean age 20.7 years, range 18-24 years; mean weight 59.3 kg) received drug. All post-dose gastrin concentrations were within the normal range (<100 pg ml(-1)). The tmax following Cysteamine bitartrate non-enteric-coated (mean and SD is 75+/-19 min) was shorter than Cysteamine bitartrate enteric-coated (220+/-74 min) (P=0.001), but only the Cmax and AUC estimates following 900 mg Cysteamine bitartrate enteric-coated were significantly greater than any of the other preparations or doses (P<0.05). One patient had GI symptoms following both 900 mg Cysteamine bitartrate non-enteric-coated and Cysteamine bitartrate enteric-coated. Conclusion: Although patient numbers were low, single high doses of Cysteamine bitartrate enteric-coated were better tolerated than similar doses of Cysteamine bitartrate non-enteric-coated in the healthy subjects and all had normal gastrin concentrations. The delayed tmax following Cysteamine bitartrate enteric-coated suggested that the cysteamine was released enterically.
A novel sustained-release Cysteamine bitartrate formulation for the treatment of cystinosis: Pharmacokinetics and safety in healthy male volunteers
Pharmacol Res Perspect 2021 Apr;9(2):e00739.PMID:33764642DOI:10.1002/prp2.739.
The strict intake regimen of Cysteamine bitartrate formulations, associated with side effects, is a concern for the treatment compliance in cystinosis therapy. Therefore, there is a need for a cysteamine formulation with an improved pharmacokinetic profile. This study investigated the pharmacokinetics, safety and tolerability of a new sustained-release cysteamine dosage form, PO-001, in healthy volunteers. This was a randomized, investigator-blinded, three-way cross-over study to compare single doses (600 mg) of PO-001 with Cystagon® (immediate-release) and Procysbi® (delayed-release). Collected blood samples were analyzed for plasma cysteamine concentrations and pharmacokinetic parameters were estimated by noncompartmental analysis. In addition, plasma cysteamine concentrations were analyzed using a population pharmacokinetic approach using NONMEM® . Pharmacokinetics showed clear sustained-release characteristics of PO-001 over time with a lower Cmax and longer Tmax compared to Cystagon® and Procysbi® . All treatment-emergent adverse events were of mild severity, with the exception of two subjects who reported moderate severity gastrointestinal problems including vomiting and diarrhea, which were related to Cystagon® intake. Population PK simulations showed a favourable PK profile based on Cmax and Ctrough concentrations at steady state. In conclusion, a single dose of 600 mg PO-001 was well tolerated with no findings of clinical concern. This new Cysteamine bitartrate formulation showed pharmacokinetics of a sustained-release formulation, which may be beneficial for the treatment of cystinosis patients. This study supports advancing this type of sustained-release formulation into a subsequent study to confirm reduced dosing frequency with efficient control of white blood cells (WBCs) cystine levels. Netherlands Trial Registry (NTR) (NL67638.056.18).
Twice-daily Cysteamine bitartrate therapy for children with cystinosis
J Pediatr 2010 Jan;156(1):71-75.e1-3.PMID:19775699DOI:10.1016/j.jpeds.2009.07.016.
Objective: Cystinosis causes renal and other organ failure. Regular 6-hourly Cysteamine bitartrate (Cystagon; Mylan, Morgantown, West Virginia) reduces intracellular cystine and the rate of organ deterioration. A formulation of cysteamine requiring less frequent dosing may improve compliance and possibly patient outcome. Methods: Enteric-release cysteamine was prepared. For a period of 1 month, patients received their regular cysteamine dose every 6 hours (stage I). The patients then underwent pharmacokinetic and pharmacodynamic studies following washout periods using single-doses of cysteamine and enteric-release cysteamine (stage II). Finally, the patients commenced regular enteric-release cysteamine therapy (stage III). Weekly trough white blood cell (WBC) cystine levels were recorded. Results: Seven children with cystinosis (mean age, 11.8 years; range, 8-17 years) who received cysteamine and enteric-release cysteamine (mean dose, 45 and 28.8 mg/kg body weight/day, respectively) had mean WBC cystine levels of 0.7+/-0.3 and 0.41+/-0.22 nmol half-cystine/mg protein in study stages I and III, respectively. Study stage II showed that the mean time (T(max)) to reach the maximum plasma cysteamine level (C(max)) was longer for enteric-release cysteamine than for cysteamine (176 minutes vs 60 minutes; P=.001), but the mean C(max) at the same dose was similar. Mean serum gastrin levels were similar after ingestion of cysteamine and enteric-release cysteamine. Conclusions: Twelve-hour enteric-release cysteamine, given at approximately 60% of the previous daily dose of cysteamine, was effective in maintaining trough WBC cystine levels within a satisfactory range.