Asunaprevir

Asunaprevir Uses, Dosage, Side Effects, Food Interaction and all others data.

Asunaprevir, also named BMS-650032, is a potent hepatitis C virus (HCV) NS3 protease inhibitor. It has been shown to have a very high efficacy in dual-combination regimens with daclatasvir in patients chronically infected with HCV genotype 1b. It was developed by Bristol-Myers Squibb Canada and approved by Health Canada on April 22, 2016. The commercialization of asunaprevir was cancelled one year later on October 16, 2017.

Studies in vitro demonstrated a significant antiviral activity in HCV replicon cell systems with an EC50 of 4nm and 1nm against the HCV genotype 1a and 1b respectively. These studies showed a limited activity against the genotypes 2 and 3. This property makes asunaprevir a highly selective anti-HCV agent that is not effective against HCV closely related virus. Asunaprevir produce robust declines in HCV RNA levels in patients with HCV genotype 1 infection.In clinical studies, it has been shown that asunaprevir is well-tolerated and the mean maximum HCV RNA level reduction from baseline was of approximately 2.87 log10 IU/ml.

Monotherapy clinical studies with asunaprevir showed a mean maximum decline of HCV RNA in the range of 0.28-2.87 log10 IU/ml when administered in increasing doses from 10-600 mg. When asunaprevir was used as a combination product, it was possible to obtain a sustained virological response (aviremia 24 weeks after completion of therapy) in 83-92% of the patients.

Asunaprevir
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Asunaprevir
Generic	Asunaprevir
Asunaprevir Other Names	Asunaprevir
Type
Formula	C₃₅H₄₆ClN₅O₉S
Weight	Average: 748.286 Monoisotopic: 747.270476492
Protein binding	Protein binding of asunaprevir is very high and it can reach more than 99% of the administered dose independently of the dose. In vitro studies with human Caco-2 cells indicated that asunaprevir is a substrate of P-gp, OATP1B1 and OATP2B1.
Groups	Approved, Investigational, Withdrawn
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Asunaprevir is an NS3 protease inhibitor used to treat hepatitis C genotype 1b.

Asunaprevir is indicated in combination with other agents for the treatment of chronic hepatitis C in adult patients with hepatitis C virus genotypes 1 or 4 and compensated liver cirrhosis.

Hepatitis C is a liver disease caused by the hepatitis C virus. The chronic state of this condition accounts for 60-80% of the cases from which the risk of cirrhosis of the liver within 20 years is of around 15-30%. The genotype 1 is the most common type of hepatitis C in the United States and the most difficult to treat.

Asunaprevir is also used to associated treatment for these conditions: Chronic Hepatitis C Genotype 1, Chronic hepatitis C genotype 4

How Asunaprevir works

Asunaprevir is a highly active HCV NS3 protease inhibitor. The genome of HCV has a positive polarity which allows it to be translated into a protein in the host cell without further transformation steps. However, the resultant protein needs to be divided by the enzyme NS3 protease into single proteins in order to be able to exert its enzymatic activity or structural role. Therefore, due to NS3 vital importance for viral replication, the inhibiting action of asunaprevir causes a robust antiviral activity.

Toxicity

Toxicity studies showed no carcinogenic nor genotoxic potential related to asunaprevir. In case of overdose, clinical studies reported no unexpected adverse events.Asunaprevir had no effects on fertility in preclinical studies. It has been shown that asunaprevir gets localized in GI tract and liver and thus, increased in hepatic transaminases were observed as well as changes in iron metabolism, decreased in serum proteins. These effects are not progressive and asunaprevir was generally well tolerated.

Food Interaction

Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of asunaprevir. Co-administration of asunaprevir with St. John's Wort is contraindicated.
Exercise caution with grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of asunaprevir.
Take with or without food.

Volume of Distribution

The registered volume of distribution at steady state is 194 L.

Elimination Route

In preclinical studies, asunaprevir showed a high liver-to-plasma AUC ratio. It is rapidly absorbed within 30 minutes of administration. Clinical pharmacokinetic studies showed a tmax of 2-4 hours. The pharmacokinetic profile act in a dose-proportional manner and in a dose of 100 mg the steady-state Cmax and AUC was 572 ng/ml and 1887 ng.h/ml. The absolute bioavailability is reported to be 9.3%. The absorption of asunaprevir is increased if it is accompanied by a high-fat diet.

Half Life

Clinical pharmacokinetic studies showed a mean terminal half-life of 15-20 hours.

Clearance

Clinical pharmacokinetic studies showed a mean oral clearance of 302-491 L/h.

Elimination Route

Asunaprevir is primarily eliminated via the feces. From the administered dose, 84% is excreted by feces mainly as metabolites and less than 1% of the dose is recovered as metabolites in the urine. The proportion of unchanged asunaprevir recovered in feces represents only 7.5% of the dose.