Valgancyclovir

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Valgancyclovir
• 英文别名: [2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-3-hydroxypropyl] 2-amino-3-methylbutanoate
• 化学式: C₁₄H₂₂N₆O₅
• 分子量: 354.36
• InChiKey: WPVFJKSGQUFQAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  167
• 氢给体数：
  4
• 氢受体数：
  7

ADMET

代谢

Valganciclovir 是一种抗病毒药物，它是 ganciclovir 的 L-缬氨酰酯（前药），以两种对映异构体的混合物形式存在。口服给药后，这两种对映异构体通过肠道和肝脏的酯酶迅速转化为 ganciclovir ...

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir that exists as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

Valganciclovir迅速水解为更昔洛韦；没有检测到其他代谢物。口服给药的放射性标记更昔洛韦（单次剂量1000毫克）的代谢物在粪便或尿液中回收的放射性中，没有一种超过1%到2%。

Valganciclovir is rapidly hydrolyzed to ganciclovir; no other metabolites have been detected. No metabolite of orally administered radiolabeled ganciclovir (1000 mg single dose) accounted for more than 1% to 2% of the radioactivity recovered in the feces or urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

静脉注射更昔洛韦与2%的患者血清ALT水平短暂轻中度升高有关。这些发作通常无症状且自行限制。CMV感染本身可以引起肝酶升高，可能是治疗期间发现的一些异常的原因。几乎没有证据表明更昔洛韦或缬更昔洛韦会导致临床上明显的肝损伤。更昔洛韦对HBV也有活性，治疗期间HBV DNA水平会下降，在治疗停止时可能会反弹，导致急性乙型肝炎的发作，这可能会出现症状且严重。

Intravenous administration of ganciclovir is associated with transient mild-to-moderate elevations in serum ALT levels in 2% of patients. These episodes have usually been asymptomatic and self-limited. CMV infection itself can cause liver enzyme elevations and may account for some abnormalities found during therapy. There is little evidence that either ganciclovir or valganciclovir can cause clinically apparent liver injury. Ganciclovir also has activity against HBV and HBV DNA levels decrease on treatment and can rebound when therapy is stopped, leading to an acute flare of hepatitis B, which can be symptomatic and severe.

来源:LiverTox

毒理性

• 相互作用

使用更昔洛韦和齐多夫定时可能发生的潜在药物相互作用（加合性血液学毒性（中性粒细胞减少，贫血））。

Potential pharmacologic interaction (additive hematologic toxicity (neutropenia, anemia)) /with concomitant use of valganciclovir and zidovudine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

使用更昔洛韦和丙磺舒可能存在潜在的药代动力学相互作用（降低肾脏清除率，增加更昔洛韦的药时曲线下面积（AUC））；监测更昔洛韦的毒性。

Potential pharmacokinetic interaction /with concomitant use of valganciclovir and probenecid/ (decreased renal clearance and increased AUC of ganciclovir); monitor for ganciclovir toxicity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

潜在药物相互作用（加性血液学毒性）/与更昔洛韦和骨髓抑制药物或放疗同时使用/。

Potential pharmacologic interactions (additive hematologic toxicity) /with concomitant use of valganciclovir and myelosuppressive agents or irradiation/.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

使用valganciclovir和mycophenolate mofetil的肾脏损害患者可能存在药代动力学相互作用（两种药物代谢物的血浆浓度增加）。

Potential pharmacokinetic interaction /with concomitant use of valganciclovir and mycophenolate mofetil/ in patients with renal impairment (increased plasma concentrations of the metabolites of both drugs).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

瓦根昔洛韦的主要消除途径是通过肾脏排泄，以肾小球滤过和主动肾小管分泌的方式将更昔洛韦排出体外。静脉给药的更昔洛韦的系统清除率为3.07 ± 0.64 mL/min/kg（n=68），而肾脏清除率为2.99 ± 0.67 mL/min/kg（n=16）。

The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion. Systemic clearance of intravenously administered ganciclovir was 3.07 + or - 0.64 mL/min/kg (n=68) while renal clearance was 2.99 + or - 0.67 mL/min/kg (n=16).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

由于伐更昔洛韦迅速转化为更昔洛韦，因此没有测定伐更昔洛韦的血浆蛋白结合率。在0.5至51微克/毫升的浓度范围内，更昔洛韦的血浆蛋白结合率为1%至2%。当静脉注射更昔洛韦时，更昔洛韦的稳态分布体积为0.703±0.134升/公斤（n=69）。在服用Valcyte片剂后，未观察到更昔洛韦AUC与体重倒数之间的相关性；因此，根据体重口服Valcyte片剂是不必要的。

Due to the rapid conversion of valganciclovir to ganciclovir, plasma protein binding of valganciclovir was not determined. Plasma protein binding of ganciclovir is 1% to 2% over concentrations of 0.5 and 51 ug/mL. When ganciclovir was administered intravenously, the steady-state volume of distribution of ganciclovir was 0.703 + or - 0.134 L/kg (n=69). After administration of Valcyte tablets, no correlation was observed between ganciclovir AUC and reciprocal weight; oral dosing of Valcyte tablets according to weight is not required.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当Valcyte片剂与高脂肪餐一起服用时，餐中含有大约600卡路里（31.1克脂肪，51.6克碳水化合物和22.2克蛋白质），剂量为每天一次875毫克，给16名HIV阳性患者服用，稳态更昔洛韦AUC增加了30%（95% CI 12%至51%），Cmax增加了14%（95% CI -5%至36%），而达到峰值血浆浓度的时间（Tmax）没有延长。Valcyte应在用餐时服用。

When Valcyte tablets were administered with a high fat meal containing approximately 600 total calories (31.1 g fat, 51.6 g carbohydrates and 22.2 g protein) at a dose of 875 mg once daily to 16 HIV-positive subjects, the steady-state ganciclovir AUC increased by 30% (95% CI 12% to 51%), and the Cmax increased by 14% (95% CI -5% to 36%), without any prolongation in time to peak plasma concentrations (Tmax). Valcyte should be administered with food.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

瓦根昔洛韦口服给药后甘昔洛韦的绝对生物利用度大约是口服甘昔洛韦的十倍（分别为60%和5.6%）。成人的药代动力学研究结果表明，餐后口服900毫克瓦根昔洛韦一次每日，提供的甘昔洛韦平均血药浓度-时间曲线下面积（0-24小时，AUC0-24小时）与静脉注射甘昔洛韦5毫克/千克一次每日相当，且超过了餐后口服甘昔洛韦1克三次每日。然而，在这些剂量下，口服瓦根昔洛韦产生的甘昔洛韦血药峰浓度低于静脉注射甘昔洛韦，血药谷浓度低于口服甘昔洛韦。这三种甘昔洛韦给药系统在峰浓度和谷浓度方面的差异在临床上的重要性，如果有的话，尚未确定。

The absolute bioavailability of ganciclovir following oral administration of valganciclovir is about tenfold higher than that following oral administration of ganciclovir (60 versus 5.6%, respectively). Results from pharmacokinetic studies in adults indicate that oral administration of valganciclovir 900 mg once daily with food provides a mean area under the plasma concentration-time curve 0-24 hour (AUC0-24 hour) for ganciclovir comparable to that following IV ganciclovir 5 mg/kg once daily and exceeding that following oral ganciclovir 1 g 3 times daily with food. However, at these dosages, oral valganciclovir produces lower peak plasma ganciclovir concentrations than IV ganciclovir, and lower trough plasma ganciclovir concentrations than oral ganciclovir. The clinical importance, if any, of these differences in peak and trough plasma drug concentrations with these 3 ganciclovir delivery systems has not been determined.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• Preparation of ester of purine derivatives
  申请人：Ramchandra Dharamaraj Rao

  公开号：US20070225305A1

  公开（公告）日：2007-09-27

  A process for the preparation of valganciclovir with triacetyl ganciclovir (V) as a starting material, comprising the following steps: selective hydrolysis, reacting with a coupling agent and a solvent, followed by hydrolysis under basic conditions and hydrogenolysis in the presence of a catalyst.

  一种以三乙酰甘昔洛韦（V）为起始原料制备瓦尔甘昔洛韦的工艺，包括以下步骤：选择性水解，与偶联剂和溶剂反应，随后在碱性条件下水解，并在催化剂存在下进行氢解。
• Compositions Containing Antiviral Compounds and Methods of Using the Same
  申请人：Cantrell Gary L.

  公开号：US20090258843A1

  公开（公告）日：2009-10-15

  The present invention is directed to compositions and methods for the treatment of various diseases, pathological disorders, and medical conditions such as viral infections and cancer. The compositions include (A) an antiviral compound or a pharmaceutically acceptable salt thereof; and (B) an agent selected from the group consisting of a substituted or unsubstituted imidazole or a pharmaceutically acceptable salt thereof; a non-steroidal anti-inflammatory agent or a pharmaceutically acceptable salt thereof; an amino acid or a pharmaceutically acceptable salt thereof; a carboxylic acid or a pharmaceutically acceptable salt thereof; a sulfonic acid or a pharmaceutically acceptable salt thereof; and a combination thereof.

  本发明涉及用于治疗各种疾病、病理障碍和医疗条件，如病毒感染和癌症的组合物和方法。所述组合物包括（A）抗病毒化合物或其药学上可接受的盐；和（B）从以下组中选择的药剂：取代或未取代的咪唑或其药学上可接受的盐；非甾体抗炎药或其药学上可接受的盐；氨基酸或其药学上可接受的盐；羧酸或其药学上可接受的盐；磺酸或其药学上可接受的盐；或其组合物。
• TRANSCRIPTIONALLY TARGETED AND CPG-FREE PLASMID FOR THERANOSTIC GENE THERAPY
  申请人：The Johns Hopkins University

  公开号：US20200140831A1

  公开（公告）日：2020-05-07

  A DNA plasmid useful for diagnostic and therapeutic gene therapy is disclosed. Improvements to gene therapy methods known in the art are provided to ensure cancer-targeting, high efficacy, and long durability of expression. The DNA plasmid is combined with compositions of polymeric nanoparticles for non-viral gene therapy to treat cancer, including hepatocellular carcinoma and prostate cancer.
• US8324381B2
  申请人：——

  公开号：US8324381B2

  公开（公告）日：2012-12-04
• [EN] COMPOSITIONS CONTAINING ANTIVIRAL COMPOUNDS AND METHODS OF USING THE SAME<br/>[FR] COMPOSITIONS CONTENANT DES COMPOSÉS ANTIVIRAUX ET LEURS PROCÉDÉS D'UTILISATION
  申请人：MALLINCKRODT INC

  公开号：WO2009129094A2

  公开（公告）日：2009-10-22

  The present invention is directed to compositions and methods for the treatment of various diseases, pathological disorders, and medical conditions such as viral infections and cancer. The compositions include (A) an antiviral compound or a pharmaceutically acceptable salt thereof; and (B) an agent selected from the group consisting of a substituted or unsubstituted imidazole or a pharmaceutically acceptable salt thereof; a non-steroidal anti inflammatory agent or a pharmaceutically acceptable salt thereof; an amino acid or a pharmaceutically acceptable salt thereof; a carboxylic acid or a pharmaceutically acceptable salt thereof; a sulfonic acid or a pharmaceutically acceptable salt thereof; and a combination thereof.