Velpatasvir is both an inhibitor and a substrate of the transporter proteins P-glycoprotein (Pgp), ABCG2, OATP1B1 and OATP1B3. It is partly degraded by the liver enzymes CYP2B6, CYP2C8 and CYP3A4. Substances that are transported or inactivated by these proteins, or interfere with them, can interact with velpatasvir. In studies, this has been found for the HIV combination efavirenz/emtricitabine/tenofovir, which reduces the area under the curve (AUC) of velpatasvir by about 50%, and the CYP3A4 and Pgp inducer rifampicin, which reduces its AUC by about 80%, rendering it likely ineffective. Digoxin is eliminated by Pgp; its AUC is increased by about 30% in combination with velpatasvir and sofosbuvir (although it is not clear which of the two is responsible for this effect).
Substances that reduce gastric acid, such as antacids, H2 blockers, and proton pump inhibitors, reduce velpatasvir AUC by 20–40%.
Velpatasvir reaches highest blood plasma levels three hours after oral intake together with sofosbuvir. Plasma protein binding is over 99.5%. It is slowly metabolised by the liver enzymes CYP2B6, CYP2C8 and CYP3A4. While monohydroxylated and demethylated metabolites have been identified in human blood plasma and faeces, over 98% of the circulating substance is velpatasvir itself.[3] 94% are excreted via the faeces, and only 0.4% via the urine. Biological half-life is about 15 hours.
