Foscarbidopa
(Synonyms: Carbidopa 4′-monophosphate) 目录号 : GC36069
Foscarbidopa (Carbidopa 4′-monophosphate) 是一种卡比多巴 (Carbidopa) 前药，是多巴胺受体的激动剂 。
Cas No.:1907685-81-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Foscarbidopa (Carbidopa 4′-monophosphate) is a prodrug of Carbidopa, acts as a dopamine receptor agonist[1][2]. dopamine receptor[2]
[1]. Benoit CARDINAL-DAVID, et al. Carbidopa and L-Dopa Prodrugs and Methods of Use. US 20160106765 A1. [2]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 32, No. 4, 2018.
| Cas No. | 1907685-81-7 | SDF | |
| 别名 | Carbidopa 4′-monophosphate | ||
| Canonical SMILES | O=P(O)(O)OC(C=CC(C[C@@](NN)(C)C(O)=O)=C1)=C1O | ||
| 分子式 | C10H15N2O7P | 分子量 | 306.21 |
| 溶解度 | H2O : 40 mg/mL (130.63 mM; ultrasonic and warming and adjust pH to 9 with 1 M NaOH 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 | 3.2657 mL | 16.3287 mL | 32.6573 mL |
| 5 mM | 0.6531 mL | 3.2657 mL | 6.5315 mL |
| 10 mM | 0.3266 mL | 1.6329 mL | 3.2657 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。
Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease
Ann Neurol 2021 Jul;90(1):52-61.PMID:33772855DOI:10.1002/ana.26073.
Objective: The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. Methods: Foslevodopa and Foscarbidopa were prepared and the equilibrium solubility and chemical stability examined in aqueous media with different values of pH. Solutions of foslevodopa/Foscarbidopa (ratios ranging from 4:1 to 20:1) were prepared by dissolving pH-adjusted lyophilized materials in water and infused s.c. in healthy volunteers for ≤72 hours. Frequent blood samples were collected to measure LD and CD exposure, and safety was monitored throughout the study. Results: Foslevodopa/Foscarbidopa (ABBV-951) demonstrates high water solubility and excellent chemical stability near physiological pH, enabling continuous s.c. infusion therapy. After s.c. infusion, a stable LD pharmacokinetic (PK) profile was maintained for ≤72 hours, and the infusion was well tolerated. Interpretation: Preparation of foslevodopa and Foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In phase 1 clinical trials, foslevodopa/Foscarbidopa demonstrates consistent and stable LD plasma exposure, supporting further studies of this treatment as a potentially transformational option for those suffering from PD. ANN NEUROL 2021;90:52-61.
Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion
J Parkinsons Dis 2021;11(4):1695-1702.PMID:34366380DOI:10.3233/JPD-212813.
Background: Foslevodopa/Foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson's disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/Foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/Foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/Foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/Foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/Foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/Foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/Foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.
Foslevodopa/Foscarbidopa subcutaneous infusion maintains equivalent levodopa exposure to levodopa-carbidopa intestinal gel delivered to the jejunum
Parkinsonism Relat Disord 2022 Apr;97:68-72.PMID:35339102DOI:10.1016/j.parkreldis.2022.03.012.
Introduction: The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/Foscarbidopa to the LD pharmacokinetics from 16-h levodopa-carbidopa intestinal gel (LCIG) followed by night-time oral LD/carbidopa (CD) doses. Methods: This was a Phase 1, open-label, randomized, 2-period crossover study conducted in 25 male and female healthy volunteers. Results: The LD exposures (Cmax0-16, AUC0-16 and AUC∞) following subcutaneous infusion of 700/35 mg foslevodopa/Foscarbidopa over 24 h were similar (<8% difference) to those of LCIG 350/87.5 mg LD/CD administered over 16 h followed by two 100/25 mg LD/CD oral doses at 18 and 21 h after the start of LCIG delivery. Conclusion: Foslevodopa/Foscarbidopa subcutaneous infusion provides levodopa exposures comparable to LCIG throughout the day. Gov identifier: Not Applicable.
Comparability of Foslevodopa/Foscarbidopa Pharmacokinetics in Healthy Asian and White Participants
Clin Pharmacol Drug Dev 2023 Apr;12(4):407-415.PMID:36394144DOI:10.1002/cpdd.1201.
This phase 1 study assessed the safety, tolerability, and pharmacokinetics of a single 24-hour continuous subcutaneous dose of foslevodopa/Foscarbidopa in healthy adult Japanese (N = 24), Han Chinese (N = 8), and White (N = 24) participants. Three doses of foslevodopa/Foscarbidopa were evaluated in healthy participants for this study: 480/24, 960/48, and 1440/72 mg/day. Serial blood samples for measurement of levodopa, carbidopa, foslevodopa, Foscarbidopa, and 3-O-methyldopa concentrations were collected for 48 hours after foslevodopa/Foscarbidopa administration. Safety and tolerability were assessed throughout the study. Point estimates for ratios of central values indicated that the exposure difference between Japanese and White participants was <10%. The maximum concentration and area under the plasma concentration-time curve for both LD and CD following foslevodopa/Foscarbidopa continuous subcutaneous infusion were comparable between Han Chinese and White participants. Point estimates for ratios of central values indicated that the exposure difference between Han Chinese and White participants was <14%. The regimens tested were generally well tolerated, and no new safety issues were identified in this study. There were no clinically meaningful differences in LD and CD exposures or pharmacokinetics following administration of foslevodopa/Foscarbidopa among White, Japanese, and Han Chinese participants.
Scalable Asymmetric Syntheses of Foslevodopa and Foscarbidopa Drug Substances for the Treatment of Parkinson's Disease
J Org Chem 2022 Feb 18;87(4):1986-1995.PMID:34280307DOI:10.1021/acs.joc.1c00905.
Foslevodopa (FLD, levodopa 4'-monophosphate, 3) and Foscarbidopa (FCD, carbidopa 4'-monophosphate, 4) were identified as water-soluble prodrugs of levodopa (LD, 1) and carbidopa (CD, 2), respectively, which are useful for the treatment of Parkinson's disease. Herein, we describe asymmetric syntheses of FLD (3) and FCD (4) drug substances and their manufacture at pilot scale. The synthesis of FLD (3) employs a Horner-Wadsworth-Emmons olefination reaction followed by enantioselective hydrogenation of the double bond as key steps to introduce the α-amino acid moiety with the desired stereochemistry. The synthesis of FCD (4) features a Mizoroki-Heck reaction followed by enantioselective hydrazination to install the quaternary chiral center bearing a hydrazine moiety.