Sibrafiban
(Synonyms: RO 48-3657) 目录号 : GC64571
Sibrafiban (RO 48-3657) 是一种 Ro 44-3888 的具有口服活性的，非肽，双重前药，是一种选择性的糖蛋白 IIb/IIIa 受体 (glycoprotein IIb/IIIa receptor) 拮抗剂。Sibrafiban 可抑制血小板聚集。
Cas No.:172927-65-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sibrafiban (RO 48-3657) is the orally active, nonpeptide, double-prodrug of Ro 44-3888 and a selective glycoprotein IIb/IIIa receptor antagonist. Sibrafiban inhibits platelet aggregation[1][2][3].
The effects of site occupancy by Sibrafiban on platelet activation are assessed using P-selectin expression, fibrinogen binding and microaggregate formation. Sibrafiban inhibits ADP and TRAP-stimulated fibrinogen binding and microaggregate formation in a concentration-dependent manner, whereas P-selectin expression is relatively unaltered. A decrease in site occupancy from peak to trough of Sibrafiban does not result in increased activation of platelets[3].
The effects of Ro 44-3888 on the platelet aggregation response to ADP (17 μmol) and on cutaneous bleeding times is determined in 8 rhesus monkeys given Sibrafiban 0.25 mg/kg/day or 0.5 mg/kg/day orally for 8 days. The maximum inhibition of ex vivo platelet aggregation and prolongation of bleeding time by Ro 44-3888 are dose dependent[1].
[1]. M Dooley, et al. Sibrafiban. Drugs. 1999 Feb;57(2):225-30; discussion 231-2.
[2]. B Wittke, et al. Pharmacokinetics and pharmacodynamics of sibrafiban alone or in combination with ticlopidine and aspirin. Br J Clin Pharmacol. 2000 Mar;49(3):231-9.
[3]. Jeffrey T Billheimer, et al. Effects of glycoprotein IIb/IIIa antagonists on platelet activation: development of a transfer method to mimic peak to trough receptor occupancy. Thromb Res. 2002 Sep 15;107(6):303-17.
| Cas No. | 172927-65-0 | SDF | Download SDF |
| 别名 | RO 48-3657 | ||
| 分子式 | C20H28N4O6 | 分子量 | 420.46 |
| 溶解度 | DMSO : 33.33 mg/mL (79.27 mM; Need ultrasonic) | 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 | 2.3783 mL | 11.8917 mL | 23.7835 mL |
| 5 mM | 0.4757 mL | 2.3783 mL | 4.7567 mL |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3783 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。
Sibrafiban
Drugs 1999 Feb;57(2):225-30; discussion 231-2.PMID:10188763DOI:10.2165/00003495-199957020-00012.
Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of Sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave MI or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of Sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with Sibrafiban include bleeding, with minor haemorrhages occurring more often than with aspirin.
Pharmacokinetics and pharmacodynamics of Sibrafiban alone or in combination with ticlopidine and aspirin
Br J Clin Pharmacol 2000 Mar;49(3):231-9.PMID:10718778DOI:10.1046/j.1365-2125.2000.049003231.x.
Aims: The purpose of this clinical study was to evaluate the effects of a ticlopidine/aspirin combination on the pharmacokinetics and pharmacodynamics of Sibrafiban and the tolerability of the combination therapy Methods: Thirty-eight healthy male volunteers were randomized to receive one of the following treatments for 7 days: Sibrafiban (n = 12), ticlopidine/aspirin (n = 12), or the combination treatment Sibrafiban/ticlopidine/aspirin (n = 14). Concentrations of the active metabolite of Sibrafiban, Ro 44-3888, in plasma and urine were determined by column-switching liquid chromatography combined with tandem mass spectrometry. The pharmacodynamics of Sibrafiban and ticlopidine/aspirin were examined by measuring the inhibition of ADP- or collagen-induced platelet aggregation. Results: The addition of ticlopidine/aspirin to Sibrafiban did not significantly alter the pharmacokinetic parameters of Ro 44-3888. the geometric mean ratio for AUC(0,12h) was 110 (95% CI 0.82, 1.22). Separately, Sibrafiban and ticlopidine/aspirin inhibited ADP-and collagen-induced platelet aggregation and the effects of the two treatments were additive. For example, the average inhibition of ADP-induced platelet aggregation over 12 h was 42% in the Sibrafiban treated group, 55% in the ticlopidine/aspirin group and 69% in the Sibrafiban/ticlopidine group. The bleeding time was prolonged in the treatments with ticlopidine/aspirin (8.1 min) and Sibrafiban/ticlopidine/aspirin (8. 6 min) compared with Sibrafiban alone (3.5 min). Conclusions: This study shows a significant pharmacodynamic interaction between Sibrafiban and ticlopidine/aspirin. Consequently, the simultaneous administration of Sibrafiban and ticlopidine/aspirin should be carefully monitored to ensure the patient's coverage with an antiplatelet drug without exposure to an excessive bleeding risk.
Sibrafiban (Genentech)
IDrugs 1999 May;2(5):460-5.PMID:16155849doi
Sibrafiban (G-7453) is an orally active non-peptide GPIIb/IIIa antagonist, under development by Genentech and Hoffmann-La Roche, and in phase III trials as an antithrombotic. Roche intends to file for marketing approval in 1999. Merrill Lynch predicts a product launch in 2001.
Pharmacokinetics and pharmacodynamics of Sibrafiban, an orally administered GP IIb/IIIa antagonist, following coadministration of aspirin and heparin
J Clin Pharmacol 2000 May;40(5):488-95.PMID:10806602DOI:10.1177/00912700022009107.
Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active GP IIb/IIIa antagonist after oral administration. This clinical investigation evaluated whether coadministration of oral aspirin or intravenous heparin would alter the pharmacokinetics or pharmacodynamics of oral Sibrafiban. Twenty-four adult subjects received two of the following four combinations: Sibrafiban alone, Sibrafiban with ASA, Sibrafiban with heparin, and Sibrafiban with ASA and heparin, separated by a 2-week washout period. Concentration profiles of active drug in citrate and EDTA plasma were unchanged with coadministration of ASA or heparin. No pharmacodynamic interaction was seen with coadministration of heparin. Inhibition of platelet aggregation increased 4% to 55%, and Ivy bleeding time increased 58% to 87% with coadministration of Sibrafiban and ASA. The combined pharmacodynamic effect of Sibrafiban and ASA may indicate a potentially greater therapeutic effect but an increased risk of bleeding when these drugs are used in combination.
Pharmacokinetics and pharmacodynamics of Sibrafiban, an orally administered IIb/IIIa antagonist, in patients with acute coronary syndrome
J Clin Pharmacol 1999 Jul;39(7):675-84.PMID:10392322DOI:10.1177/00912709922008317.
Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active IIb/IIIa antagonist following oral administration. Pharmacokinetics (PK) and pharmacodynamics (PD) of oral Sibrafiban and its metabolites were evaluated in patients postacute coronary syndrome receiving once- or twice-daily Sibrafiban for up to 28 days at several dose levels. Mean peak concentrations of Sibrafiban were < 5 ng/mL. Peak single prodrug concentrations occurred 1.7 +/- 1.0 (mean +/- SD) hours after Sibrafiban dosing. Total apparent plasma clearance of the single prodrug was 40 +/- 15 L/h, and the elimination half-life was 2.3 +/- 0.8 hours. Mean values of the steady-state pharmacokinetics for total concentrations of the active drug over all doses were: time to peak plasma concentration, 5.0 +/- 1.7 hours; apparent clearance, 13.9 +/- 3.9 L/h; and half-life, 11.0 +/- 2.8 hours. Once-daily dosing resulted in high peak-trough excursions in active drug concentrations: trough concentrations were 21% +/- 6% of peak. Twice-daily dosing resulted in an AUC for the active drug on Day 28 that was 168% +/- 36% of that on Day 1, and steady-state trough concentrations were 54% +/- 10% of peak with sustained inhibition of platelet aggregation. Dose-adjusted steady-state active drug concentrations increased with increasing age and with decreasing renal function and body weight.