Dasabuvir API Manufacturers & Suppliers

Dasabuvir (CAS number 1132935-63-7) is an oral direct-acting antiviral agent indicated for the treatment of chronic Hepatitis C virus (HCV) infection, specifically genotypes 1a and 1b. It is approved for use in combination with other antiviral agents such as ombitasvir, paritaprevir, ritonavir, and optionally ribavirin, typically formulated as a fixed-dose combination marketed under the tradename Viekira Pak. The approved regimen targets patients including those with compensated cirrhosis, with the goal of achieving sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks post-treatment, which correlates with long-term clinical benefits such as reduced hepatic fibrosis progression and decreased hepatocellular carcinoma risk.

Pharmacologically, dasabuvir is a non-nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase. It selectively binds to the palm domain of NS5B, inducing a conformational change that inhibits polymerase elongation activity, thereby preventing viral RNA replication. This binding is distinct from nucleoside inhibitors as it occurs outside the enzyme’s active site. The compound exhibits potent in vitro activity against genotype 1a and 1b viral strains, with EC50 values in the low nanomolar range; however, its mechanism confers limited activity against other genotypes due to low conservation of the binding domain.

Dasabuvir undergoes hepatic metabolism mainly via cytochrome P450 isoforms including CYP2C8, CYP2D6, and CYP3A4, and is also a substrate for P-glycoprotein and breast cancer resistance protein (BCRP/ABCG2) transporters. Consequently, potential drug interactions mediated by cytochrome P450 enzymes and transporter proteins warrant consideration in clinical use. Safety data indicate a generally favorable profile in approved combinations, though monitoring for hepatic function and drug-drug interactions is advised. There is limited data on use in severe hepatic impairment.

From a sourcing perspective, the quality and purity of the dasabuvir API must conform to regulatory standards ensuring consistent polymorphic form, impurity profile, and stability. Given its critical role in combination regimens, reliable supply chains and validated analytical methods are essential to support manufacturing and regulatory submissions. Manufacturers should ensure compliance with current Good Manufacturing Practices (cGMP) and relevant pharmacopeial standards to meet global regulatory requirements.