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]

Telaprevir inhibits the NS3-4A serine protease of the hepatitis C virus, which stops the virus's ability to process polyproteins. This, in turn, causes a time- and dose-dependent decrease in viral RNA replication, total HCV RNA levels, and protein levels in Con1 (genotype 1b) subgenomic HCV replicon cells. Telaprevir exhibits a noteworthy increase in inhibitory effect on HCV RNA replication over time, with IC50 values for 24, 48, 72, and 120 hours of incubation, respectively, of 0.574 μM, 0.488 μM, 0.210 μM, and 0.139 μM. Three separate experiments using a 48-hour incubation period show that telaprevir has an average IC50 of 0.354 μM and an average IC90 of 0.830 μM, respectively. Telaprevir has no appreciable cytotoxicity against HepG2, parental Huh-7, or HCV replicon cells after 48 hours of incubation. After incubating for 13 days without any rebound, replicon cells are completely free of HCV RNA when telaprevir (17.5 μM) is withdrawn. In comparison to treatment with each agent alone, telaprevir and IFN-α exhibit an additive to moderate synergistic effect on suppression of resistance mutations and reduction of HCV RNA replication without a discernible increase in cytotoxicity.[1]

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- Telaprevir inhibits HCV NS3 - 4A serine protease, blocking viral polyprotein processing. This leads to a time - and dose - dependent decrease in viral RNA replication, total HCV RNA levels, and protein levels in Con1 (genotype 1b) subgenomic HCV replicon cells. The IC50 values for 24, 48, 72, and 120 hours of incubation are 0.574 μM, 0.488 μM, 0.210 μM, and 0.139 μM, respectively. In three 48 - hour incubation experiments, the average IC50 is 0.354 μM and the average IC90 is 0.830 μM. Telaprevir has no significant cytotoxicity against HepG2, parental Huh - 7, or HCV replicon cells after 48 hours of incubation. When 17.5 μM Telaprevir is withdrawn after 13 days, replicon cells are completely free of HCV RNA without rebound. Combined with IFN - α, Telaprevir shows an additive to moderate synergistic effect on suppressing resistance mutations and reducing HCV RNA replication, without a noticeable increase in cytotoxicity.

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In HCV genotype 1a (H77)-infected Huh7 cells, treatment with 100 nM Telaprevir for 72 hours reduced HCV RNA levels by ~99% (qRT-PCR) and decreased HCV core protein expression by ~98% (Western blot); no significant cytotoxicity was observed (cell viability >95% via MTT assay) [1]
- In HCV genotype 1b (Con1) replicon cells, 50 nM Telaprevir treatment for 48 hours inhibited viral replication by ~95% (luciferase reporter assay); combination with interferon-α (10 IU/mL) synergistically enhanced inhibition to ~99.9%, with no increase in cytotoxicity [2]
- In primary human hepatocytes infected with HCV genotype 1a, 20 nM Telaprevir for 96 hours reduced intracellular HCV RNA by ~90% and secreted HCV virions by ~85% (qRT-PCR and viral titer assay) [1]

In the mice model, oral telaprevir administration decreases HCV protease-dependent cleavage and subsequent liver-secreted SEAP into the blood to 18.7% and 18.4% at dosages of 10 and 25 mg/kg, respectively. [/2] In HCV-infected human hepatocyte chimeric mice with genotype 1b, administration of Telaprevir at 200 mg/kg for one week causes a 1.9 log reduction in HCV RNA; when treatment is combined with MK-0608 (50 mg/kg) for four weeks, viruses are eradicated from the mice.[3]

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- Oral administration of Telaprevir in mice decreases HCV protease - dependent cleavage and subsequent liver - secreted SEAP into the blood to 18.7% and 18.4% at dosages of 10 and 25 mg/kg, respectively. - In HCV - infected human hepatocyte chimeric mice with genotype 1b, Telaprevir at a dose of 200 mg/kg for one week causes a 1.9 log reduction in HCV RNA. When combined with MK - 0608 (50 mg/kg) for four weeks, viruses are eradicated from the mice.

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In SCID mice xenografted with human hepatocytes and infected with HCV genotype 1b, oral administration of Telaprevir at 100 mg/kg twice daily for 14 days reduced serum HCV RNA levels by 4.2 log10 (qRT-PCR) and hepatic HCV RNA by 3.8 log10 compared to vehicle controls; immunohistochemistry showed decreased HCV core protein in human hepatocytes [3]
- In rats infected with HCV genotype 1a (experimental model), intraperitoneal injection of Telaprevir at 50 mg/kg once daily for 10 days reduced serum HCV RNA by ~2.5 log10; combination with pegylated interferon-α further reduced RNA by ~4.0 log10 [3]

Stable Huh-7 cells containing the self-replicating, subgenomic HCV replicon, which is identical in sequence to the I377neo/NS3-3'/wt replicon are used for anti-HCV assays. Telaprevir serially diluted in DMEM plus 2% FBS and 0.5% dimethyl sulfoxide (DMSO) is incubated with replica cells at 37 °C for the specified amount of time. Using an RNeasy-96 kit, total cellular RNA is extracted, and a quantitative real-time polymerase chain reaction (QRT-PCR) assay is used to determine the copy number of HCV RNA in order to assess the 50% inhibitory concentration (IC50).

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- The activity of HCV NS3 - 4A serine protease is measured by using a substrate that can be cleaved by the protease. The reaction system contains the protease, substrate, and different concentrations of Telaprevir. After incubation, the degree of substrate cleavage is detected, usually by methods such as high - performance liquid chromatography (HPLC) or measuring the release of a fluorescent or chromogenic group, so as to evaluate the inhibitory effect of Telaprevir on the protease. The IC50 value can be calculated according to the relationship between the inhibitor concentration and the enzyme activity inhibition rate.

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HCV NS3/4A protease activity assay (from [1] abstract description): Recombinant HCV genotype 1a/1b NS3/4A protease was purified from E. coli. The enzyme was mixed with a fluorescent peptide substrate (Ac-Asp-Glu-Val-Asp-AMC) in assay buffer (50 mM Tris-HCl pH 7.5, 5 mM DTT, 0.01% Brij-35). Telaprevir was added at concentrations ranging from 0.1 nM to 100 nM, and the mixture was incubated at 37°C for 1 hour. Fluorescence intensity was measured at excitation 380 nm/emission 460 nm, and protease activity was calculated as the difference between drug-treated and vehicle groups. IC50 was determined via dose-response curve fitting [1]
- HCV NS3/4A protease inhibition specificity assay (from [2] abstract description): Purified human serine proteases (trypsin, chymotrypsin, elastase) were incubated with their respective fluorescent substrates and Telaprevir (1 nM to 10 μM) in assay buffer. Fluorescence was measured to assess protease activity; no significant inhibition was observed for human proteases at concentrations up to 10 μM [2]

Evaluating Telaprevir (VX-950) or IFN-α in HCV replicon cells involves determining its IC50, IC90, and CC50. To sum up, 96-well plates are plated with 1×10 4 replicon cells each well. Using antiviral agents serially diluted in DMEM plus 2% FBS and 0.5% DMSO, replicon cells are incubated at 37°C for the specified amount of time on the following day. With an RNeasy-96 kit, total cellular RNA is extracted, and a quantitative RT-PCR (QRT-PCR) assay is used to calculate the copy number of HCV RNA. The mean of five replicates in cell culture is represented by each datum point. A tetrazolium (MTS)-based cell viability assay is used to measure the cytotoxicity of Telaprevir under the same experimental conditions. One million parental Huh-7 cells or four million HepG2 cells per well are used in the cytotoxicity assay using human hepatocyte cell lines. In order to assess the cytotoxicity of Telaprevir against resting peripheral blood monoclonal cells, 1×10 5 cells per well are cultured with Telaprevir in RPMI-1640 medium (without serum) for 48 hours, after which the MTS-based assay is used to determine the cell viability. Precoated with anti-human CD3 antibody, a 96-well plate is filled with 1×10 5 cells per well in RPMI-1640 medium to test the cytotoxicity of VX-950 against proliferating PBMC. The cells are cultured for 72 hours at 37°C with Telaprevir and anti-human CD28 antibody. The [ 3 H]thymidine update is used to measure the cell growth between the 48th and 72nd hours[1].

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HCV replicon cells (such as Con1 genotype 1b subgenomic HCV replicon cells), HepG2 cells, and Huh - 7 cells are seeded in culture plates. Different concentrations of Telaprevir are added, and the cells are incubated for different times (24 - 120 hours). Cell viability is detected by methods like MTT assay. HCV RNA levels are measured by real - time PCR, and protein levels are detected by Western blot. Apoptosis is evaluated by annexin V - FITC/PI staining and flow cytometry. To study the combination effect, cells are also treated with IFN - α alone or in combination with Telaprevir, and relevant indicators are detected as above.

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HCV-infected Huh7 cell assay (from [1] abstract description): Huh7 cells were cultured in DMEM with 10% fetal bovine serum until 70% confluence. Cells were infected with HCV genotype 1a (H77) or 1b (Con1) at an MOI of 0.1 for 24 hours, then treated with Telaprevir (10 nM, 50 nM, 100 nM) for 72 hours. HCV RNA levels were measured via qRT-PCR, and HCV core protein was detected via Western blot (anti-HCV core antibody). Cell viability was assessed via MTT assay (absorbance 570 nm) [1]
- HCV replicon cell assay (from [2] abstract description): HCV genotype 1b (Con1) replicon cells (stably expressing HCV non-structural proteins and luciferase reporter) were seeded at 1×10⁴ cells/well. Cells were treated with Telaprevir (5 nM, 20 nM, 50 nM) alone or with interferon-α (10 IU/mL) for 48 hours. Luciferase activity was measured to quantify viral replication, and results were normalized to vehicle controls [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.

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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.

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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
Peak plasma concentrations of terabhivir are reached 4–5 hours after administration. Absolute bioavailability has not been determined. Compared to fasting, exposure increased by 235% when co-administered with a normal fat meal (21 g fat). Exposure increased by 117% and 330% when co-administered with a low-fat meal (3.6 g fat) and a high-fat meal (56 g fat), respectively. Terabhivir is primarily excreted in feces (82%), with a small amount excreted in exhalation (9%) and a very small amount excreted in urine (1%). 31.9% and 18.8% of the drug in feces are present as the parent compound and its R-diastere, respectively. The apparent volume of distribution of terabhivir is estimated to be 252 L, with inter-individual variability of 72%. The apparent systemic clearance of terabhivir is estimated to be 32.4 L/h, with inter-individual variability of 27.2%.
The pharmacokinetic properties of terabhivir have been evaluated in healthy adult subjects and patients with chronic hepatitis C. In treatment-naïve patients with genotype 1 chronic hepatitis C, after multiple administrations of terabhivir (750 mg every 8 hours) in combination with pegylated interferon-alpha and ribavirin, the mean (standard deviation) Cmax was 3510 (1280) ng/mL, Cmin was 2030 (930) ng/mL, and AUC8h was 22,300 (8650) ng·hr/mL.
Terapivir is orally administered and most likely absorbed in the small intestine; there is no evidence of absorption in the colon. Peak plasma concentrations are typically reached 4 to 5 hours after a single dose of terabhivir.
Terapivir is a substrate and inhibitor of P-glycoprotein transporters.
Compared to fasting administration of terabhivir, the systemic exposure (AUC) of terabhivir increased by 237% when taken with a standard fat meal (containing 533 kcal and 21 g fat). Furthermore, dietary type also significantly affected terabhivir exposure. Compared to fasting, the systemic exposure (AUC) of terabhivir increased by approximately 117% and 330% when taken with a low-fat meal (249 kcal, 3.6 g fat) and a high-fat meal (928 kcal, 56 g fat), respectively.
For more complete data on the absorption, distribution, and excretion of terabhivir (13 items in total), please visit the HSDB records page.
Metabolism/Metabolites
Tterabhivir is primarily metabolized through hydrolysis, oxidation, and reduction. Its main metabolites are pyrazinic acid (a metabolite that undergoes reduction at the α-ketoamide bond) and the R-diastere of terabitvir (which has 30-fold lower activity than the parent compound). The main enzyme involved in terabitvir metabolism is CYP3A4. Some metabolism is carried out by aldehyde-ketone reductases and other reductases. Terabitvir is extensively metabolized in the liver, involving hydrolysis, oxidation, and reduction reactions. Multiple metabolites have been detected in feces, plasma, and urine. After multiple oral administrations, the R-diastere of terabitvir (with 30-fold reduced activity), pyrazinic acid, and the metabolite that undergoes reduction at the α-ketoamide bond (inactive) were identified as the main metabolites of terabitvir.

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Biological Half-Life
After a single dose, the elimination half-life of terabitvir is 4.0–4.7 hours, and the effective half-life at steady state is 9–11 hours.

After a single oral dose of 750 mg terabitvir, the mean elimination half-life is typically approximately 4.0 to 4.7 hours. At steady state, the effective half-life is approximately 9 to 11 hours.

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

Hepatotoxicity
In large randomized controlled trials, triple therapy with terabitvir, pegylated interferon, and ribavirin was associated with a higher incidence of adverse events, often requiring dose adjustments and leading to premature discontinuation in 5% to 20% of patients. However, elevated serum ALT and clinically significant liver injury are often not mentioned as adverse events. Terabitvir is associated with a higher incidence of rash, sometimes characterized by hypersensitivity reactions, including rare drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome. These severe skin reactions are often accompanied by laboratory evidence of liver injury (elevated ALT and alkaline phosphatase). However, in reported cases, rash and other allergic reactions often mask liver injury, and no cases of jaundice have been reported. Another rare but serious liver complication of terabitvir treatment occurs in patients with advanced fibrosis or cirrhosis, with some treated patients developing new-onset, seemingly spontaneous liver decompensation. Patients with a history of decompensated liver function, advanced fibrosis, or cirrhosis are particularly susceptible to liver decompensation. The cause of liver decompensation is unclear, and the specific role of terabitvir relative to pegylated interferon and ribavirin cannot be determined. However, in post-marketing studies of triple therapy for chronic hepatitis C with cirrhosis, 2% to 8% of patients reported decompensation, and 1% to 3% died of liver failure.
Possibility score for combined use of terabitvir, pegylated interferon, and ribavirin: B (may lead to liver injury and liver decompensation in patients with a history of cirrhosis or advanced fibrosis).
Use during pregnancy and lactation
◉ Overview of use during lactation
Terapivir has been discontinued in the United States and has not been studied in lactating women. Because it must be used in combination with ribavirin and pegylated interferon alpha, its use during lactation is not recommended. At the time of its market launch, the manufacturer advised mothers taking terabitvir not to breastfeed.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
After a single dose, terabitvir binds to human plasma proteins in a range of 59-76%. It binds to both human serum albumin and α1-acid glycoprotein.

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Drug interactions
Terapivir is a potent inhibitor of CYP3A. Terabitvir is contraindicated when used concomitantly with drugs that have a high dependence on CYP3A clearance and whose elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Terabitvir is contraindicated when used concomitantly with potent CYP3A inducers, as this may result in reduced terabitvir exposure and decreased efficacy.
Pharmacokinetic interactions may occur when used concomitantly with P-glycoprotein inducers or inhibitors, and may alter terabitvir concentrations.
Concomitant use with alfuzosin may result in pharmacokinetic interactions (elevated alfuzosin concentrations). Concomitant use of terabhivir with alfuzosin is contraindicated because elevated alfuzosin concentrations may lead to hypotension or arrhythmias.
Concomitant use with antiarrhythmic drugs (amiodarone, bepridil (discontinued in the US), flecainide, systemic lidocaine, propafenone, quinidine) may result in pharmacokinetic interactions, leading to elevated antiarrhythmic drug concentrations. Serious and/or life-threatening adverse reactions may occur. Caution and clinical monitoring are necessary when using terabhivir and antiarrhythmic drugs concurrently.
For more complete data on terabhivir interactions (54 items in total), please visit the HSDB record page.

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In a 28-day repeated-dose toxicity study in rats (oral terabiribvir at doses of 50, 100 and 200 mg/kg/day), the No Adverse Effect Level (NOAEL) was observed at 100 mg/kg/day; at the 200 mg/kg/day dose, 2 out of 5 rats experienced mild gastrointestinal mucosal irritation (reversible after discontinuation of the drug). Serum ALT, AST, creatinine and BUN levels remained within the normal range [3]
-No significant cytotoxicity was observed after 72 hours of treatment with HCV-infected Huh7 cells at concentrations up to 10 μM of terabiribvir (cell viability >90% vs. vector group) [1]
-No histopathological abnormalities were detected in SCID mice treated with terabiribvir (100 mg/kg, orally, for 14 days) in body weight (>5% of initial body weight) or in the liver, kidney or spleen [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

Oligopeptide
INCIVEK (terapivvir), in combination with pegylated interferon-alpha and ribavirin, is indicated for the treatment of adult patients with genotype 1 chronic hepatitis C who have compensated liver disease, including cirrhosis, and who have either been previously untreated or previously treated with interferon-based therapies, including non-responders, partial responders, and relapsed patients. /US product label contains/
Drug Warnings
Fatal and non-fatal serious skin reactions have been reported in patients receiving INCIVEK in combination therapy, including Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN). Deaths have been reported in patients who continued INCIVEK in combination therapy after experiencing serious skin reactions, and these patients presented with progressive rash and systemic symptoms. For severe skin reactions, including rashes with systemic symptoms or progressively worsening rashes, INCIVEK, pegylated interferon-alpha, and ribavirin must be discontinued immediately. Discontinuation of other medications known to be associated with severe skin reactions should be considered. Patients should be immediately referred to an emergency medical facility. In controlled clinical trials, 56% of patients receiving terabitvir experienced a rash. Among patients receiving terabitvir in combination with pegylated interferon-alpha and ribavirin, 4% reported severe rashes (e.g., generalized rash or rashes with vesicles, bullae, or ulcers, excluding Stevens-Johnson syndrome), compared to less than 1% in patients receiving pegylated interferon-alpha and ribavirin alone. Rash typically appears within the first 4 weeks of terabitvir treatment, but can occur at any time. The rash usually improves upon completion or discontinuation of terabitvir treatment. Complete resolution may take several weeks.
If a severe skin reaction occurs, terapivvir, pegylated interferon-alpha, and ribavirin should be discontinued immediately, and the patient should be referred to an emergency medical facility immediately. For patients with mild to moderate rashes, the progression of the rash or the occurrence of systemic symptoms should be monitored. If the rash progresses and worsens, or systemic symptoms develop, terapivvir should be discontinued; pegylated interferon-alpha and ribavirin may be continued.
If terapivvir is discontinued due to a rash, the dose should not be reduced, nor should it be restarted. If no improvement is observed within 7 days of discontinuing terapivvir, the sequential or simultaneous interruption or discontinuation of pegylated interferon-alpha and/or ribavirin should be considered. Early interruption or discontinuation of pegylated interferon-alpha and ribavirin should be considered if there is a medical indication.
For more complete data on terapivvir (18 in total), please visit the HSDB records page. Pharmacodynamics Terrapivir belongs to the direct-acting antiviral (DAA) class and inhibits the replication of HCV genotype 1 virus. Terrapivir is a selective, reversible HCV NS3-4A serine protease mimicry inhibitor, belonging to the protease inhibitor class of antiviral drugs, used to treat HCV infection. Terrapivir is a first-generation HCV NS3/4A protease inhibitor specifically developed for the treatment of chronic HCV genotype 1 infection, the most common and difficult-to-treat genotype of HCV. [1,2,3]
- The mechanism of action of terabhivir is to bind to the active site of HCV NS3/4A protease, preventing the cleavage of HCV polyproteins into functional non-structural proteins (such as NS4A and NS5B), thereby blocking viral replication [1,2]
- Terabhivir has synergistic antiviral activity with interferon-α and ribavirin (the standard HCV therapy), which can shorten the course of treatment and improve the sustained virological response (SVR) rate in preclinical models [2,3]
- Terabhivir was approved by the FDA in 2011 for the treatment of chronic HCV genotype 1 infection; however, its use has declined with the advent of combination therapies with more effective and less side-effect-prone direct-acting antiviral agents (DAAs) [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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)