Sorivudine
(Synonyms: 索立夫定,BV-araU) 目录号 : GC39552
Sorivudine (BV-araU) 是一种口服活性的，合成的嘧啶核苷抗代谢 (pyrimidine nucleoside antimetabolite) 药物。Sorivudine 的抗病毒活性来自某些 DNA 病毒中存在的特定胸苷激酶 (thymidine kinase) 选择性转化为核苷酸，从而反过来会干扰病毒 DNA 合成 (DNA synthesis)。
Cas No.:77181-69-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sorivudine (BV-araU) is an orally active synthetic pyrimidine nucleoside antimetabolite drug. Sorivudine derives its antiviral activity from selective conversion by a specific thymidine kinase present in certain DNA viruses to nucleotides, which can in turn interfere with viral DNA synthesis[1].
[1]. Diasio RB, et al. Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br J Clin Pharmacol. 1998 Jul;46(1):1-4. [2]. Whitley RJ, et al. Sorivudine: a potent inhibitor of varicella zoster virus replication.Adv Exp Med Biol. 1996;394:41-4.
| Cas No. | 77181-69-2 | SDF | |
| 别名 | 索立夫定,BV-araU | ||
| Canonical SMILES | O=C1NC(C(/C=C/Br)=CN1[C@H]2[C@H]([C@@H]([C@@H](CO)O2)O)O)=O | ||
| 分子式 | C11H13BrN2O6 | 分子量 | 349.13 |
| 溶解度 | DMSO: 250 mg/mL (716.07 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 | 2.8643 mL | 14.3213 mL | 28.6426 mL |
| 5 mM | 0.5729 mL | 2.8643 mL | 5.7285 mL |
| 10 mM | 0.2864 mL | 1.4321 mL | 2.8643 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。
Sorivudine: a promising drug for the treatment of varicella-zoster virus infection
Neurology 1995 Dec;45(12 Suppl 8):S73-5.PMID:8545030DOI:10.1212/wnl.45.12_suppl_8.s73.
Sorivudine provides a unique nucleoside analog with significantly enhanced both in vitro and in vitro activity and enhanced oral bioavailability. Early indications from controlled studies indicate that Sorivudine therapy is superior to acyclovir for the treatment of localized zoster in individuals with HIV infection and adults with chicken pox. However, these studies await peer evaluation. Importantly, recent experience in Japan indicates administration of Sorivudine with 5-fluorouracil (5-FU) is contraindicated. Sorivudine inhibits dihydropyrimidine dehydrogenase, which is required for the metabolism of 5-FU. As a consequence, toxic levels of 5-FU accumulate in the plasma and have led to the deaths of nearly 30 patients in Japan. One might question, as these data unfold, the relative value of drugs with such enhanced in vitro activity and oral bioavailability as compared with standard therapeutic agents. Should accelerated healing occur, but not as dramatically as would have been anticipated from the in vitro data, unique approaches to the management of herpes zoster will need to be developed if further improvement is desired. Regardless, Sorivudine appears superior to acyclovir for acceleration of cutaneous healing and, importantly, can be administered once daily in significantly smaller concentrations. These findings in and of themselves should allow for licensure of the compound in other developed societies.
Sorivudine: a potent inhibitor of varicella zoster virus replication
Adv Exp Med Biol 1996;394:41-4.PMID:8815706DOI:10.1007/978-1-4757-9209-6_5.
Sorivudine provides a unique nucleoside analog with significantly enhanced both in vitro as in vitro activity toward VZV and enhanced oral bioavailability, as compared with existing antivirals. Early indications from controlled studies, while not peer reviewed, indicate that Sorivudine therapy is superior to acyclovir for the treatment of localized zoster in individuals with HIV infection and chicken pox in adults. These studies await peer evaluation. One might question, as these data unfold, the relative clinical value of antivirals with such enhanced in vitro activity and oral bioavailability as compared to standard compounds. Should these drugs induce accelerated healing, but not as dramatically as would have been anticipated from the in vitro data, new approaches to the management of herpes zoster will need to be developed if further improvement is desired. Despite this provision, Sorivudine therapy does appear to result in significantly accelerated healing of cutaneous zoster as compared to acyclovir, and Sorivudine can be administered once daily in a dose that is one-hundredth that of acyclovir, and less than one tenth of the doses of valacuyclovir or famciclovir. These findings in and of themselves should allow for licensure of the compound in developed societies.
Sorivudine versus acyclovir for treatment of dermatomal herpes zoster in human immunodeficiency virus-infected patients: results from a randomized, controlled clinical trial. Collaborative Antiviral Study Group/AIDS Clinical Trials Group, Herpes Zoster Study Group
Antimicrob Agents Chemother 1998 May;42(5):1139-45.PMID:9593141DOI:10.1128/AAC.42.5.1139.
The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of Sorivudine [1-beta-D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered Sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus Sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, Sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017). In a univariate analysis, there was a trend favoring Sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.
The effect of Sorivudine on dihydropyrimidine dehydrogenase activity in patients with acute herpes zoster
Clin Pharmacol Ther 1997 May;61(5):563-73.PMID:9164418DOI:10.1016/S0009-9236(97)90136-3.
Objective: Bromovinyl-uracil (BVU) is the principal metabolite of Sorivudine, a potent anti-zoster nucleoside. BVU binds to, and irreversibly inhibits, the enzyme dihydropyrimidine dehydrogenase (DPD). The objective of this study was to assess the time course of recovery of DPD activity after oral administration of Sorivudine in patients with herpes zoster and to correlate restoration of DPD activity and levels of uracil with the elimination of Sorivudine and its metabolite BVU from the circulation. Methods: Sorivudine was given orally as 40 mg once-daily doses for 10 consecutive days to a total of 19 patients with herpes zoster. Serum Sorivudine, BVU, and circulating uracil and DPD activity in peripheral blood mononuclear cells (PBMCs) were determined before, during, and after administration of Sorivudine. Results: BVU was eliminated from the circulation within 7 days after the last Sorivudine dose. DPD activity in PBMCs, which was completely suppressed in 18 of the 19 subjects and markedly suppressed in the remaining subject during administration of Sorivudine, recovered to baseline levels within 19 days after the last dose of Sorivudine in all subjects and within 14 days in all but one of the subjects. The restoration of DPD activity was temporally associated with elimination of BVU from the circulation. The elevated uracil concentrations produced by inhibition of DPD activity fell rapidly after cessation of Sorivudine administration and also were temporally associated with elimination of BVU from the circulation. The time course of recovery of DPD activity in three patients with renal impairment was similar to that of the other subjects. Conclusions: This study indicates that Sorivudine therapy is associated with a profound depression of DPD activity. Recovery of DPD activity occurred within 4 weeks of the completion of Sorivudine therapy, which indicates that fluorinated pyrimidines may be safely administered 4 weeks after completion of Sorivudine therapy.
[Lethal drug interactions of the new antiviral, Sorivudine, with anticancer prodrugs of 5-fluorouracil]
Yakugaku Zasshi 1997 Nov;117(10-11):910-21.PMID:9414600DOI:10.1248/yakushi1947.117.10-11_910.
In 1993 eighteen Japanese patients with cancer and herpes zoster, a viral disease, died from interactions of the new oral antiviral drug, Sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), with oral anticancer prodrugs of 5-fluorouracil (5-FU) within 40 d after SRV was approved by the Japanese government and began to be used clinically. Before the death, most of these patients had severe symptoms of toxicity, including diarrhea with bloody flux and marked decreases in white blood cell and platelet counts. All of these patients received SRV daily for several days while being administered long-term anticancer chemotherapy with one of the oral 5-FU prodrugs. There was no acute toxic symptom in patients who received SRV alone or SRV and the other types of anticancer drugs. A toxicokinetic study was carried out using rats to investigate the mechanism of the acute death in the patients caused by drug interactions between SRV and 5-FU prodrugs. Rats were orally coadministered SRV with tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil), a 5-FU prodrug that most of the patients were considered to receive before the death. All the rats receiving SRV and FT once daily showed extremely elevated levels of 5-FU in the plasma and tissues, including bone marrow and small intestines, and died within 10 d, while the animals given the same repeated dose of SRV or FT alone were still alive over 20 d without any appreciable toxic symptom. Before their death, there were a marked damage of bone marrow, a marked atrophy of intestinal membrane mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia as reported for the patients. Data obtained by in vivo and in vitro studies indicated that (E)-5-(2-bromovinyl)uracil (BVU), generated from SRV by the gut flora and absorbed through the intestinal membrane, was reduced in the presence of NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key enzyme regulating the tissue 5-FU levels from FT, bound covalently to DPD as a suicide inhibitor, and markedly retarded the catabolism of 5-FU. An irreversible inactivation by BVU of rat and human DPDs, expressed in E. coli for the latter, was observed in the presence of NADPH with their purified preparations in a manner reciprocal to radiolabelling of the enzyme proteins with [14C]BVU. SRV showed no inhibitory effect on the rat and human DPDs in the presence of NADPH.