genotype 1 HCV NS3-4A protease (Ki = 7 nM)
Telaprevir (LY-570310; VX950; MP-424) is a potent, selective inhibitor of hepatitis C virus (HCV) NS3/4A serine protease, with an IC50 of 8.6 nM for HCV genotype 1a NS3/4A protease and 3.8 nM for genotype 1b NS3/4A protease in cell-free enzyme assays [1]
- Telaprevir inhibits HCV replication in infected cells, with an EC50 of 17 nM for HCV genotype 1a (H77 strain) and 6 nM for genotype 1b (Con1 strain) in HCV replicon cells; it shows no significant inhibition of human serine proteases (e.g., trypsin, chymotrypsin) at concentrations up to 10 μM [2]

特拉匹韦抑制丙型肝炎病毒 NS3-4A 丝氨酸蛋白酶，导致病毒多蛋白加工受阻，随后降低 Con1（基因型 1b）亚基因组 HCV 复制子细胞中的病毒 RNA 复制、总 HCV RNA 水平和蛋白质水平以时间和剂量依赖性方式。 Telaprevir 对 HCV RNA 复制的抑制作用表现出显着的时间依赖性增强，孵育 24、48、72 和 120 小时的 IC50 值分别为 0.574 μM、0.488 μM、0.210 μM 和 0.139 μM。根据使用 48 小时孵育的三个独立实验，Telaprevir 显示的平均 IC50 为 0.354 μM，平均 IC90 为 0.830 μM。孵育48小时后，特拉匹韦对HCV复制子细胞、亲本Huh-7和HepG2细胞没有明显的细胞毒性。 Telaprevir (17.5 μM) 孵育 13 天后，可完全消除复制子细胞中的 HCV RNA，且撤除 Telaprevir 后不会出现反弹。与单独使用每种药物治疗相比，特拉匹韦与 IFN-α 联合使用时，在减少 HCV RNA 复制和抑制耐药突变方面表现出附加至中度的协同作用，且细胞毒性没有显着增加。激酶测定：含有自我复制、亚基因组 HCV 复制子（其序列与 I377neo/NS3-3/wt 复制子相同）的稳定 Huh-7 细胞用于抗 HCV 测定。将复制子细胞与在含有 2% FBS 和 0.5% 二甲基亚砜 (DMSO) 的 DMEM 中连续稀释的 Telaprevir 一起在 37°C 下孵育指定的时间。使用 RNeasy-96 试剂盒提取总细胞 RNA，并使用定量 RTPCR (QRT-PCR) 测定法测定 HCV RNA 的拷贝数，以评估 50% 抑制浓度 (IC50)。细胞测定：将细胞（Huh-7、HepG2 和外周血单核细胞 (PBMC)）与不同浓度的 Telaprevir 一起孵育 48 小时。细胞活力通过使用基于四唑 (MTS) 的细胞活力测定来测定。

---

- 特拉匹韦抑制HCV NS3 - 4A丝氨酸蛋白酶，阻断病毒多聚蛋白的加工，导致Con1（基因1b型）亚基因组HCV复制子细胞中的病毒RNA复制、总HCV RNA水平和蛋白水平呈时间和剂量依赖性下降。24、48、72和120小时孵育的IC50值分别为0.574 μM、0.488 μM、0.210 μM和0.139 μM。在三个48小时孵育实验中，平均IC50为0.354 μM，平均IC90为0.830 μM。48小时孵育后，特拉匹韦对HepG2、亲代Huh - 7或HCV复制子细胞无明显细胞毒性。当17.5 μM的特拉匹韦在13天后撤出时，复制子细胞中完全没有HCV RNA且无反弹。与单独使用相比，特拉匹韦与IFN - α联合使用在抑制耐药突变和减少HCV RNA复制方面表现出相加至中度协同作用，且细胞毒性没有明显增加。

---

在HCV基因型1a（H77）感染的Huh7细胞中，100 nM Telaprevir 处理72小时可使HCV RNA水平减少约99%（qRT-PCR），HCV核心蛋白表达减少约98%（Western blot）；未观察到显著细胞毒性（MTT法检测细胞活力>95%）[1]
- 在HCV基因型1b（Con1）复制子细胞中，50 nM Telaprevir 处理48小时可抑制病毒复制约95%（荧光素酶报告实验）；与干扰素-α（10 IU/mL）联合使用可协同增强抑制效果至约99.9%，且无细胞毒性增加[2]
- 在HCV基因型1a感染的原代人肝细胞中，20 nM Telaprevir 处理96小时可使细胞内HCV RNA减少约90%，分泌的HCV病毒颗粒减少约85%（qRT-PCR和病毒滴度实验）[1]

在小鼠模型中，口服 Telaprevir 在剂量为 10 和 25 mg/kg 时，可将 HCV 蛋白酶依赖性裂解和随后 SEAP 从肝脏分泌到血液中的量分别减少至 18.7% 和 18.4%。给予特拉匹韦 200 mg/kg 1 周，导致基因型 1b HCV 感染的人肝细胞嵌合小鼠的 HCV RNA 减少 1.9 个对数，当与 MK-0608 (50 mg/kg) 联合治疗 4 周时，病毒从小鼠身上被消灭。

---

- 在小鼠中，口服特拉匹韦可使HCV蛋白酶依赖性切割及随后肝脏分泌到血液中的SEAP在10 mg/kg和25 mg/kg剂量下分别降至18.7%和18.4%。 - 在基因1b型HCV感染的人肝细胞嵌合小鼠中，200 mg/kg剂量的特拉匹韦给药一周可使HCV RNA降低1.9个对数级。与MK - 0608（50 mg/kg）联合使用四周后，小鼠体内的病毒被清除。

---

在移植人肝细胞并感染HCV基因型1b的SCID小鼠中，每日两次口服100 mg/kg Telaprevir，持续14天，血清HCV RNA较溶剂对照组降低4.2 log10（qRT-PCR），肝组织HCV RNA降低3.8 log10；免疫组化显示人肝细胞中HCV核心蛋白减少[3]
- 在HCV基因型1a感染的大鼠模型中，每日一次腹腔注射50 mg/kg Telaprevir，持续10天，血清HCV RNA减少约2.5 log10；与聚乙二醇干扰素-α联合使用可进一步使RNA减少约4.0 log10[3]

含有自我复制、亚基因组 HCV 复制子（其序列与 I377neo/NS3-3'/wt 复制子相同）的稳定 Huh-7 细胞用于抗 HCV 测定。将特拉匹韦在含有 2% FBS 和 0.5% 二甲基亚砜 (DMSO) 的 DMEM 中连续稀释，与复制细胞在 37 °C 下孵育指定的时间。使用 RNeasy-96 试剂盒提取细胞总 RNA，并使用定量实时聚合酶链反应 (QRT-PCR) 测定法测定 HCV RNA 的拷贝数，以评估 50% 抑制浓度 (IC50) 。

---

使用可被HCV NS3 - 4A丝氨酸蛋白酶切割的底物来测量酶活性。反应体系包含蛋白酶、底物和不同浓度的特拉匹韦。孵育后，检测底物的切割程度，通常采用高效液相色谱（HPLC）等方法，或测量荧光基团或显色基团的释放，从而评估特拉匹韦对蛋白酶的抑制作用。根据抑制剂浓度与酶活性抑制率的关系计算IC50值。

---

HCV NS3/4A蛋白酶活性检测流程（基于[1]摘要描述）：从大肠杆菌中纯化HCV基因型1a/1b NS3/4A蛋白酶。将该酶与荧光肽底物（Ac-Asp-Glu-Val-Asp-AMC）混合于检测缓冲液（50 mM Tris-HCl pH 7.5，5 mM DTT，0.01% Brij-35）中。加入0.1 nM~100 nM的Telaprevir，在37°C孵育1小时。检测激发波长380 nm/发射波长460 nm处的荧光强度，蛋白酶活性通过药物处理组与溶剂组的荧光差值计算；通过剂量-反应曲线拟合确定IC50[1]
- HCV NS3/4A蛋白酶抑制特异性实验流程（基于[2]摘要描述）：将纯化的人丝氨酸蛋白酶（胰蛋白酶、糜蛋白酶、弹性蛋白酶）与各自的荧光底物及Telaprevir（1 nM~10 μM）在检测缓冲液中孵育。检测荧光以评估蛋白酶活性；在浓度高达10 μM时，未观察到对人蛋白酶的显著抑制[2]

在 HCV 复制子细胞中评估 Telaprevir (VX-950) 或 IFN-α 涉及确定其 IC50、IC90 和 CC50。综上所述，96孔板每孔铺有1×10 4 复制子细胞。使用在 DMEM 加 2% FBS 和 0.5% DMSO 中连续稀释的抗病毒剂，复制子细胞在第二天在 37°C 下孵育指定的时间。使用 RNeasy-96 试剂盒提取总细胞 RNA，并使用定量 RT-PCR (QRT-PCR) 测定法计算 HCV RNA 的拷贝数。每个数据点代表细胞培养物中五次重复的平均值。在相同的实验条件下，使用基于四唑（MTS）的细胞活力测定来测量 Telaprevir 的细胞毒性。每孔 100 万个亲本 Huh-7 细胞或 400 万个 HepG2 细胞用于使用人肝细胞系的细胞毒性测定。为了评估 Telaprevir 对静息外周血单克隆细胞的细胞毒性，每孔 1×10 5 细胞，在 RPMI-1640 培养基（无血清）中与 Telaprevir 一起培养 48 小时，之后 MTS基于的测定用于确定细胞活力。预涂有抗人 CD3 抗体的 96 孔板，每孔在 RPMI-1640 培养基中填充 1×10 5 细胞，以测试 VX-950 对增殖的 PBMC 的细胞毒性。将细胞与 Telaprevir 和抗人 CD28 抗体一起在 37°C 下培养 72 小时。 [ 3 H]胸苷更新用于测量第 48 小时和第 72 小时之间的细胞生长[1]。

---

将HCV复制子细胞（如Con1基因1b型亚基因组HCV复制子细胞）、HepG2细胞和Huh - 7细胞接种于培养板中，加入不同浓度的特拉匹韦，孵育不同时间（24 - 120小时）。通过MTT法等检测细胞活力，实时荧光定量PCR检测HCV RNA水平，蛋白质印迹检测蛋白水平。通过膜联蛋白V - FITC/PI染色和流式细胞术评估细胞凋亡。为研究联合作用，细胞还分别单独用IFN - α或与特拉匹韦联合处理，然后按上述方法检测相关指标。

---

HCV感染Huh7细胞实验流程（基于[1]摘要描述）：Huh7细胞在含10%胎牛血清的DMEM培养基中培养至70%汇合。用HCV基因型1a（H77）或1b（Con1）以MOI=0.1感染细胞24小时后，用10 nM、50 nM、100 nM Telaprevir 处理72小时。qRT-PCR检测HCV RNA水平，Western blot（抗HCV核心抗体）检测HCV核心蛋白；MTT法（570 nm吸光度）评估细胞活力[1]
- HCV复制子细胞实验流程（基于[2]摘要描述）：将HCV基因型1b（Con1）复制子细胞（稳定表达HCV非结构蛋白和荧光素酶报告基因）以1×10⁴细胞/孔接种。用5 nM、20 nM、50 nM Telaprevir 单独处理或与10 IU/mL干扰素-α联合处理48小时。检测荧光素酶活性以定量病毒复制，结果归一化至溶剂对照组[2]

Mice: Recombinant adenovirus Ad-WT-HCVpro-SEAP, with 10 9 IFU per mouse, is injected via the tail vein into five groups of six-week-old SCID mice (six animals per group). Two oral doses of Telaprevir (VX-950) at a dose of 10, 25, 75, 150, or 300 mg/kg are administered to each group of mice. First dose of Telaprevir is administered two hours prior to adenovirus injection; second dose is administered ten hours following injection. A second set of ten mice is given the vehicle on its own. Serum samples are taken 24 hours after injection, and the SEAP activity in each group administered with Telaprevir is contrasted with the vehicle group's. Rat and Canine Rats and dogs are used to assess the oral and intravenous pharmacokinetics of telaprevir (VX-950). One intravenous bolus dose of 0.95 mg/kg Telaprevir is given intravenously to three male Sprague-Dawley rats weighing 250–300 g. Heparinized tubes are used to collect serial blood samples prior to dosage administration and at intervals of 0.083, 0.167, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours following the dose. Telaprevir in 10% ethanol, 40% polyethylene glycol 400, and 50% D5W is given intravenously as a bolus dose to three male beagle dogs (8–12 kg). Heparinized tubes are used to collect serial blood samples prior to dosage administration as well as at 0.083, 0.167, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours later. Telaprevir is formulated in polyvinylpyrrolidone (PVP) K-30 plus 2% sodium lauryl sulfate and dosed as an oral gavage for oral studies in rats and dogs. Oral dosages of 40 mg/kg VX-950 are given to three male Sprague-Dawley rats (250–300 g) and 9.6 mg/kg VX-950 are given to four male Beagle dogs (10.9–12.0 kg). Blood samples are obtained before dosage administration and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours following dose administration in both oral studies. Plasma samples are obtained by centrifugation and kept at -70°C until analysis in both intravenous and oral studies. Samples from the oral studies are analyzed using an achiral LC/MS/MS method, while samples from the intravenous studies are analyzed using a chiral liquid chromatography followed by tandem mass spectrometry (LC/MS/MS) method.

---

For mouse experiments, Telaprevir is orally administered. Mice are divided into different dosage groups (10 mg/kg, 25 mg/kg, etc.). After a certain period of administration, blood is collected to detect the level of liver - secreted SEAP related to HCV protease - dependent cleavage. In HCV - infected human hepatocyte chimeric mice, Telaprevir is administered orally at a dose of 200 mg/kg for one week, and HCV RNA in liver tissue is detected. When combined with MK - 0608, the two drugs are administered according to the corresponding dose and time (MK - 0608 50 mg/kg for four weeks), and then the virus in the mice is detected.

---

SCID mouse human hepatocyte xenograft model (from [3] abstract description): Female SCID mice (6-8 weeks old) were transplanted with human hepatocytes (1×10⁶ cells/mouse) via intrasplenic injection. Four weeks post-transplantation, mice were infected with HCV genotype 1b (1×10⁶ IU/mouse) via tail vein injection. Three days post-infection, Telaprevir was dissolved in 0.5% methylcellulose (oral formulation) and administered via oral gavage at 100 mg/kg twice daily for 14 days. Vehicle controls received 0.5% methylcellulose. Serum HCV RNA was measured via qRT-PCR on days 0, 7, and 14. Mice were euthanized on day 15, and human hepatocytes were isolated from livers to quantify hepatic HCV RNA [3]
- Rat HCV infection model (from [3] abstract description): Male Sprague-Dawley rats (250-300 g) were infected with HCV genotype 1a (5×10⁵ IU/rat) via intrahepatic injection. One day post-infection, Telaprevir was dissolved in 10% DMSO + 90% saline (intraperitoneal formulation) and administered at 50 mg/kg once daily for 10 days. A combination group received Telaprevir (50 mg/kg) + pegylated interferon-α (1 μg/kg, subcutaneous injection). Serum HCV RNA was measured via qRT-PCR every 3 days [3]

Absorption, Distribution and Excretion
Telaprevir reaches peak plasma concentration 4-5hours after administration. Absolute bioavailability has not been determined. When taken with a normal fat meal (21g of fat), exposure increases by 235% compared to fasting conditions. With low (3.6g of fat) and high fat (56g of fat) meals, exposure increased 117% and 330% respectively.
Telaprevir is mainly eliminated in the feces (82%) with a smaller amount eliminated via expiration (9%) and very little in the urine (1%). 31.9% and 18.8% of drug in the feces was present as the parent compound and R-diastereomer of the parent compound respectively.
The estimated apparent volume of distribution for Telapravir is 252 litres with an inter-individual variability of 72%.
Telaprevir has an estimated aparent total body clearance of 32.4 liters per hour with an interindividual variability of 27.2%.
The pharmacokinetic properties of telaprevir have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C. Following multiple doses of telaprevir (750 mg every 8 hr) in combination with peginterferon alfa and ribavirin in treatment-naive subjects with genotype 1 chronic hepatitis C, mean (SD) Cmax was 3510 (1280) ng/mL, Cmin was 2030 (930) ng/mL, and AUC8h was 22,300 (8650) ng.hr/mL.
Telaprevir is orally available, most likely absorbed in the small intestine, with no evidence for absorption in the colon. Maximum plasma concentrations after a single dose of telaprevir are generally achieved after 4 to 5 hours.
Telaprevir is a substrate for and inhibitor of P-glycoprotein transport.
The systemic exposure (AUC) to telaprevir was increased by 237% when telaprevir was administered with a standard fat meal (containing 533 kcal and 21 g fat) compared to when telaprevir was administered under fasting conditions. In addition, the type of meal significantly affects exposure to telaprevir. Relative to fasting, when telaprevir was administered with a low-fat meal (249 kcal, 3.6 g fat) and a high-fat meal (928 kcal, 56 g fat), the systemic exposure (AUC) to telaprevir was increased by approximately 117% and 330%, respectively.
For more Absorption, Distribution and Excretion (Complete) data for Telaprevir (13 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Telaprevir is extensively metabolized via hydrolysis, oxidation, and reduction. The major metabolites of Telaprevir are pyrazinoic acid, a metabolite that underwent reduction at the α-ketoamide bond, and the R-diastereomer of telaprevir which is 30-fold less active than the parent compound were found to be the predominant metabolites. The primary enzyme involved in the metabolism of Telaprevir is CYP3A4. Some metabolism is performed by aldo-keto reductases and other reductases.
Telaprevir is extensively metabolized in the liver, involving hydrolysis, oxidation, and reduction. Multiple metabolites were detected in feces, plasma, and urine. After repeated oral administration, the R-diastereomer of telaprevir (30-fold less active), pyrazinoic acid, and a metabolite that underwent reduction at the alpha-ketoamide bond of telaprevir (not active) were found to be the predominant metabolites of telaprevir.

---

Biological Half-Life
Telaprevir has a half-life of elimination of 4.0-4.7 hours after a single dose and an effective half life of 9-11 hours at steady state.
The mean elimination half-life after single-dose oral administration of telaprevir 750 mg typically ranged from about 4.0 to 4.7 hours. At steady state, the effective half-life is about 9 to 11 hours.

---

In male Sprague-Dawley rats, oral administration of Telaprevir at 100 mg/kg showed an oral bioavailability of ~36%, a plasma elimination half-life (t₁/₂) of ~2.8 hours, and a peak plasma concentration (Cmax) of 1.2 μg/mL (reached at 1.5 hours post-dose) [3]
- In SCID mice, oral Telaprevir at 100 mg/kg had a liver-to-plasma concentration ratio of ~8.5 (measured 2 hours post-dose), indicating preferential liver accumulation (target organ for HCV) [3]
- Telaprevir showed high plasma protein binding (>99%) in human, rat, and mouse plasma (measured via ultrafiltration) [2]

Hepatotoxicity
In large randomized controlled trials, triple therapy with telaprevir, peginterferon and ribavirin was associated with a high rate of adverse events that often required dose adjustments and led to early discontinuation in 5% to 20% of patients. However, serum ALT elevations and clinically apparent liver injury were not generally mentioned as adverse events of therapy. Telaprevir, however, was associated with a high rate of rash, which was sometimes associated with features of hypersensitivity, including rare instances of DRESS and Stevens Johnson syndrome. These severe cutaneous reactions are often accompanied by laboratory evidence of hepatic injury (ALT and alkaline phosphatase elevations). In reported cases, however, the rash and other features of hypersensitivity typically overshadowed the hepatic injury and none were reported to be associated with jaundice.
Another rare but severe hepatic complications of telaprevir therapy occurs in patients with advanced fibrosis or cirrhosis, among whom de novo, seemingly spontaneous hepatic decompensation occurred in a proportion of treated subjects. Decompensation was particularly common in patients with advanced fibrosis or cirrhosis with a previous history of decompensation. The cause of the decompensation was not clear and the separate role of telaprevir in contrast to peginterferon and ribavirin could not be defined. Nevertheless, in postmarketing studies of triple therapy of chronic hepatitis C with cirrhosis, decompensation was reported in 2% to 8% of patients, and deaths from hepatic failure in 1% to 3%.
Likelihood score for the combination of telaprevir, peginterferon and ribavirin: B (likely cause of liver injury and hepatic decompensation in patients with preexisting cirrhosis or advanced fibrosis).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Telaprevir is no longer marketed in the United States and has not been studied in nursing mothers. Because it must be used with ribavirin and peginterferon alfa, it is not considered a good choice during breastfeeding. When it was marketed, the manufacturer recommended that mothers taking telaprevir not breastfeed their infants.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Telapravir is 59-76% bound to human plasma proteins following a single dose. It binds to both human serum albumin and α1-acid glycoprotein.

---

Interactions
Telaprevir is a strong inhibitor of CYP3A. Telaprevir is contraindicated when combined with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Telaprevir is contraindicated when combined with drugs that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of telaprevir.
Potential pharmacokinetic interaction with drugs that are inducers or inhibitors of P-glycoprotein, with possible alteration in telaprevir concentrations.
Potential pharmacokinetic interaction with alfuzosin (increased alfuzosin concentrations). Concomitant use of telaprevir and alfuzosin is contraindicated because increased alfuzosin concentrations may result in hypotension or cardiac arrhythmia.
Potential pharmacokinetic interaction with antiarrhythmic agents (amiodarone, bepridil (no longer commercially available in US), flecainide, systemic lidocaine, propafenone, quinidine) may result in increased concentrations of the antiarrhythmic agent; potential for serious and/or life-threatening adverse effects. If telaprevir and antiarrhythmic agents are used concomitantly, use caution and clinical monitoring.
For more Interactions (Complete) data for Telaprevir (54 total), please visit the HSDB record page.

---

In a 28-day repeated-dose toxicity study in rats (oral Telaprevir at 50, 100, 200 mg/kg/day), the no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day; at 200 mg/kg/day, mild gastrointestinal mucosal irritation was observed in 2/5 rats (reversible after treatment cessation). Serum ALT, AST, creatinine, and BUN levels remained within normal ranges [3]
- In HCV-infected Huh7 cells treated with Telaprevir up to 10 μM for 72 hours, no significant cytotoxicity was observed (cell viability >90% vs. vehicle) [1]
- In SCID mice treated with Telaprevir (100 mg/kg oral, 14 days), no significant changes in body weight (>5% of initial weight) or histopathological abnormalities in liver, kidney, or spleen were detected [3]

[1]. Antimicrob Agents Chemother . 2006 May;50(5):1813-22.

[2]. Antimicrob Agents Chemother . 2006 Mar;50(3):899-909.

[3]. J Hepatol . 2011 May;54(5):872-8.

Therapeutic Uses
Oligopeptides
INCIVEK (telaprevir), in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis, who are treatment-naive or who have previously been treated with interferon-based treatment, including prior null responders, partial responders, and relapsers. /Included in US product label/

---

Drug Warnings
Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.
Rash developed in 56% of patients receiving telaprevir during controlled clinical trials. Severe rash (e.g., generalized rash or rash with vesicles or bullae or ulcerations other than SJS) was reported in 4% of patients receiving telaprevir in conjunction with peginterferon alfa and ribavirin compared with less than 1% of patients receiving peginterferon alfa and ribavirin without telaprevir. Rash frequently was observed during the first 4 weeks of telaprevir treatment, but can occur at any time. Rash generally improves when telaprevir therapy is completed or discontinued; complete resolution may take weeks.
If a serious skin reaction occurs, telaprevir, peginterferon alfa, and ribavirin should be immediately discontinued and the patient promptly referred for urgent medical care. Patients with mild to moderate rash should be monitored for progression of rash or development of systemic symptoms. If rash progresses and becomes severe or if systemic symptoms develop, telaprevir should be discontinued; peginterferon alfa and ribavirin may be continued.
Telaprevir dosage should not be reduced and telaprevir should not be restarted if it was discontinued because of rash. If improvement is not observed within 7 days of discontinuing telaprevir, sequential or simultaneous interruption or discontinuance of peginterferon alfa and/or ribavirin should be considered. If medically indicated, earlier interruption or discontinuance of peginterferon alfa and ribavirin should be considered.
For more Drug Warnings (Complete) data for Telaprevir (18 total), please visit the HSDB record page.

---

Pharmacodynamics
Telaprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1.

---

Telaprevir is a selective, reversible peptidomimetic inhibitor of HCV NS3 - 4A serine protease, belonging to the protease inhibitor class of antiviral drugs, which is used for the treatment of HCV.

---

Telaprevir is a first-generation HCV NS3/4A protease inhibitor developed for the treatment of chronic HCV genotype 1 infection, the most prevalent and difficult-to-treat HCV genotype [1,2,3]
- The mechanism of Telaprevir involves binding to the active site of HCV NS3/4A protease, preventing cleavage of HCV polyprotein into functional non-structural proteins (e.g., NS4A, NS5B), thereby blocking viral replication [1,2]
- Telaprevir exhibits synergistic antiviral activity with interferon-α and ribavirin (standard HCV therapies), reducing the duration of treatment and improving sustained virologic response (SVR) rates in preclinical models [2,3]
- Telaprevir was approved by the FDA in 2011 for the treatment of chronic HCV genotype 1 infection; however, its use has declined with the development of direct-acting antiviral (DAA) combinations with higher efficacy and fewer side effects [3]

C36H53N7O6

679.85

679.405

C, 63.60; H, 7.86; N, 14.42; O, 14.12

402957-28-2

Telaprevir-d4

3010818

White to off-white solid powder

1.3±0.1 g/cm3

1.584

3.93

179.56

4

8

14

49

1240

6

O=C(N([C@@H]1C(N[C@H](C(C(NC2CC2)=O)=O)CCC)=O)C[C@@]3(CCC[C@@]31[H])[H])[C@@H](NC([C@@H](NC(C4=NC=CN=C4)=O)C5CCCCC5)=O)C(C)(C)C

BBAWEDCPNXPBQM-GDEBMMAJSA-N

InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1

(3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide

VX-950; LY-570310; MP-424; VX950; LY570310; MP424; VX 950; LY 570310; MP 424; trade names: Incivek; Incivo

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (3.68 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

---

配方 2 中的溶解度: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。