Tecarfarin
(Synonyms: 1,1,1,3,3,3-六氟-2-甲基丙烷-2-基4-[(4-羟基-2-氧代-2H-苯并吡喃-3-YL)甲基]苯甲酸酯,ATI-5923) 目录号 : GC38857
Tecarfarin (ATI-5923) 是一种具有口服活性，非竞争性维生素 K 环氧化物还原酶 (VKOR) 拮抗剂，损害维生素K依赖性凝血因子 II，VII，IX 和 X 的活化。Tecarfarin具有抗血栓形成活性。
Cas No.:867257-26-9
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
Tecarfarin (ATI-5923) is an orally active and non-competitive vitamin K epoxide reductase (VKOR) antagonist, and impairs the activation of the vitamin K-dependent clotting factors II, VII, IX and X[1]. Tecarfarin has the antithrombotic activity [2].
[1]. Hobl EL, et al. Tecarfarin: A Novel Vitamin K Antagonist. Thromb Haemost. 2017 Nov;117(11):2009-2011. [2]. Bowersox SS, et al. Antithrombotic activity of the novel oral anticoagulant, Tecarfarin [Sodium 3-[4-((1,1,1,3,3,3-hexafluoro-2-methylpropan-2-yloxy) carbonyl) benzyl]-2-oxo-2H-chromen-4-olate] in animal models. Thromb Res. 2010 Nov;126(5):e383-8.
| Cas No. | 867257-26-9 | SDF | |
| 别名 | 1,1,1,3,3,3-六氟-2-甲基丙烷-2-基4-[(4-羟基-2-氧代-2H-苯并吡喃-3-YL)甲基]苯甲酸酯,ATI-5923 | ||
| Canonical SMILES | O=C(OC(C(F)(F)F)(C)C(F)(F)F)C1=CC=C(CC2=C(O)C3=CC=CC=C3OC2=O)C=C1 | ||
| 分子式 | C21H14F6O5 | 分子量 | 460.32 |
| 溶解度 | DMSO: 250 mg/mL (543.10 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 | 2.1724 mL | 10.862 mL | 21.724 mL |
| 5 mM | 0.4345 mL | 2.1724 mL | 4.3448 mL |
| 10 mM | 0.2172 mL | 1.0862 mL | 2.1724 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。
Pharmacokinetics of Tecarfarin and Warfarin in Patients with Severe Chronic Kidney Disease
Thromb Haemost 2017 Nov;117(11):2026-2033.PMID:28933798DOI:10.1160/TH16-10-0815.
Chronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and Tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (n = 13) were matched to healthy volunteers (HVs) (n = 10). Each subject was randomized to either warfarin 10 mg or Tecarfarin 30 mg and was later crossed over to the other drug. PK parameters were measured following each drug. Mean plasma concentrations of (S)-warfarin and (R,S)-warfarin were higher (44 and 27%, respectively) in the subjects with CKD than in the healthy subjects. Both of these values fell outside of the 90% confidence interval of equivalence. For Tecarfarin, the difference was less than 15% higher. Elimination half-life (t1/2) increased by 20% for (S)-warfarin and by 8% for (R,S)-warfarin and decreased by 8% for Tecarfarin. The mean plasma concentration for Tecarfarin's inactive metabolite ATI-5900 increased by approximately eightfold. CKD increased the effect of CYP2C9 genetic variation on (S)-warfarin and (R,S)-warfarin metabolism. Tecarfarin exposure was similar between the HVs and the CKD subjects regardless of CYP2C9 genotype. There were neither serious adverse events (SAEs) nor treatment-emergent adverse events (TEAEs) for any subject in the study. CKD inhibits metabolism of (S)-warfarin and (R,S)-warfarin, but not Tecarfarin. The safety of repeated dosing of Tecarfarin in CKD patients remains unknown. However, if the PK findings of this single-dose study are present with repeated dosing, Tecarfarin may lead to dosing that is more predictable than warfarin in CKD patients who require anticoagulation therapy.
Pharmacokinetics and pharmacodynamics of Tecarfarin, a novel vitamin K antagonist oral anticoagulant
Thromb Haemost 2017 Apr 3;117(4):706-717.PMID:28180234DOI:10.1160/TH16-08-0623.
Tecarfarin is a vitamin K antagonist (VKA) with reduced propensity for drug interactions. To evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety of Tecarfarin, we performed single ascending dose (SAD) (n=66), multiple ascending dose (MAD) (n=43), and Tecarfarin versus warfarin (n=28) studies in human volunteers. In the SAD, Tecarfarin was administered to 5 of 6 subjects (1 received placebo) in each of 11 cohorts. AUC0-∞ exhibited linearity and dose proportionality. Elimination T1/2 ranged from 87-136 hours (h) across all doses. In the MAD, Tecarfarin was administered to 5 of 6 volunteers in each of 7 cohorts. The starting dose was continued until the subject's INR reached the target range (TR) of 1.7 to 2.0. Dosing was down-titrated if the TR was achieved. Elimination T1/2 ranged from 107-140 h. Doses <10 mg had insignificant effect on INR. Higher doses raised INRs and required down-titration to maintain the TR. Steady state INR dosing was 10-20 mg. INR declined promptly after discontinuation. In the comparative study, subjects received Tecarfarin or warfarin and dose titrated to a TR of 1.5-2.0. Mean dose after TR was achieved was 13.9 mg (range 10.0-25.5 mg) for Tecarfarin and 5.3 mg (range 2.5-9.0 mg) for warfarin. At similar INR levels, the concentration of coagulation factors II, VII, IX, and X were similar for Tecarfarin and warfarin. Tecarfarin was tolerated well without serious adverse events in all three studies.
Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants
J Clin Pharmacol 2011 Apr;51(4):561-74.PMID:20622200DOI:10.1177/0091270010370588.
Comparative pharmacokinetics of vitamin K epoxide reductase antagonists Tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open-label, single-center drug interaction study. Twenty healthy adult participants were randomized 1:1 to receive approximately equipotent single oral doses of Tecarfarin (50 mg) or warfarin (17.5 mg). Following 7 days of baseline serial blood level collections, each participant received oral fluconazole 400 mg daily for 21 days. A second identical single oral dose of Tecarfarin or warfarin was given 14 days after starting fluconazole with serial pharmacokinetic sampling. Key pharmacokinetic parameters C(max), t(max), AUC(0-168), apparent clearance, and t(1/2) demonstrated no tecarfarin-fluconazole interaction but a strong warfarin-fluconazole interaction. The ratio of log-transformed mean AUC(0-168) with versus without fluconazole for Tecarfarin was 91.2% (90% confidence interval [CI]: 83.3-99.8) and for racemic warfarin was 213% (90% CI: 202-226). The 90% CI was entirely within the standard 80% to 125% bioequivalence interval for Tecarfarin but well outside the bioequivalence interval for warfarin, confirming a clinically significant pharmacokinetic interaction between warfarin and fluconazole. In contrast, Tecarfarin pharmacokinetics were apparently unchanged by fluconazole.
A randomised, double blind comparison of Tecarfarin, a novel vitamin K antagonist, with warfarin. The EmbraceAC Trial
Thromb Haemost 2016 Aug 1;116(2):241-50.PMID:27173100DOI:10.1160/TH15-11-0910.
Tecarfarin is a novel vitamin K antagonist that is metabolised by carboxyl estererase, thereby eliminating the variability associated with cytochrome-mediated metabolism. EmbraceAC was designed to compare the quality of anticoagulation with Tecarfarin and warfarin as determined by time in therapeutic range (TTR). In this phase 2/3 randomised and blinded trial, 607 patients with indications for chronic anticoagulation were assigned to warfarin (n=304) or Tecarfarin (n=303). Dosing of study drugs was managed by a centralised dose control centre, which had access to genotyping. The primary analysis tested superiority of Tecarfarin over warfarin for TTR. Patients were recruited between May 12, 2008 and May 12, 2009. TTR with Tecarfarin and warfarin were similar (72.3 % and 71.5 %, respectively; p=0.51). In those taking CYP2C9 interacting drugs, the TTR on Tecarfarin (n=92) was similar to that on warfarin (n=87, 72.2 % and 69.9 %, respectively; p=0.15). In patients with mechanical heart valves, the TTR of Tecarfarin (n=42) was similar to that of warfarin (n=42, 68.4 % and 66.3 %, respectively; p=0.51). The same was true for the TTR in patients with any CYP2C9 variant allele and on CYP2C9-interacting drugs (Tecarfarin, n=24, 76.5 % vs warfarin, n=31, 69.5 %; p=0.09). There was no difference in thromboembolic or bleeding events. In conclusion, superiority of Tecarfarin over warfarin for TTR was not demonstrated. The TTR with Tecarfarin was similar to that with well-controlled warfarin and Tecarfarin appeared to be safe and well tolerated with few major bleeding and no thrombotic events. Favourable trends in certain subpopulations make Tecarfarin a promising oral anticoagulant that deserves further study.
Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial
Am J Cardiovasc Drugs 2023 Jan;23(1):101-112.PMID:36622539DOI:10.1007/s40256-022-00562-5.
Background: Tecarfarin (ATI-5923), a structural analog of warfarin, was designed to provide more uniform and stable anticoagulation. Objective: We aimed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Tecarfarin when administered in multiple ascending doses (MADs) to healthy Chinese volunteers. Methods: Forty healthy Chinese volunteers were enrolled into four sequential cohorts (10, 20, 30, and 40 mg), with 10 subjects in each cohort. Participants in the MAD study for each sequential cohort were dose-titrated to achieve the target international normalized ratio (INR 1.7-2.0) for 14 days. Safety and tolerability were assessed throughout the study. Results: The pharmacokinetic and pharmacodynamic profile of Tecarfarin was investigated in a healthy Chinese population. Dose titration of Tecarfarin was necessary to keep the INR in the target range in all subjects in the 20, 30 and 40 mg cohorts and a few subjects (n = 3) in the 10 mg cohort. Tecarfarin was well tolerated without serious adverse events. Only one treatment-related adverse event (hematochezia) resulted in early withdrawal from the MAD 40 mg cohort. Conclusion: Tecarfarin was well-tolerated by Chinese volunteers. Dose titration was needed for Tecarfarin doses larger than 20 mg to keep the INR in the target range. Registration: ClinicalTrials.gov identifier: NCT04627116.