Dacatec Mechanism of Action

Therapeutic category: Antiviral.
Pharmacology: Daclatasvir is an inhibitor of nonstructural protein 5A (NS5A), a multifunctional protein that is an essential component of the hepatitis C virus (HCV) replication complex. Daclatasvir inhibits both viral RNA replication and virion assembly. Identification of NS5A as the drug target was based on inhibitor-binding and mapping, inhibitor-induced resistant mutations and crystal structure modelling. Results indicate that Daclatasvir acts at the N-terminus of the protein.
The pharmacokinetic properties of Daclatasvir were evaluated in healthy adult subjects and in patients with chronic HCV. Following multiple oral doses of Daclatasvir 60 mg once daily in combination with peginterferon alfa and ribavirin in treatment-naive patients with genotype 1 chronic HCV, the geometric mean (CV%) Daclatasvir Cmax was 1534 (58) ng/ml, AUC 0-24h was 14122 (70) ng•h/ml, and Cmin was 232 (83) ng/ml.
Daclatasvir administered as a tablet was readily absorbed following multiple oral doses with peak plasma concentrations occurring between 1 and 2 hours.
Absorption: Daclatasvir Cmax, AUC, and Cmin increased in a near dose-proportional manner. Steady state was achieved after 4 days of once-daily administration. At the 60 mg dose, exposure to Daclatasvir was similar between healthy subjects and HCV-infected patients.
In vitro and in vivo studies showed that Daclatasvir is a substrate of P-gp. The absolute bioavailability of the tablet formulation is 67%.
Effect of food on oral absorption: In healthy subjects, administration of Daclatasvir 60 mg tablet after a high-fat meal decreased Daclatasvir Cmax and AUC by 28% and 23%, respectively, compared with administration under fasting conditions. Administration of Daclatasvir 60 mg tablet after a light meal resulted in no reduction in Daclatasvir exposure.