TABLE 3.

Metabolism and transporter effects of direct-acting antivirals

Direct-acting antiviral	Metabolism	Transporter effects
Sofosbuvir	Hepatic; forms active nucleoside analog triphosphate GS461203	P-gp and BCRP substrate
Sofosbuvir-ledipasvira	Slow oxidative metabolism via unknown mechanism	P-gp and BCRP substrate Inhibits P-gp, BCRP, OATP1B1, OATP1B3, and bile salt export pump
Sofosbuvir-velpatasvira	Hepatic via CYP2B6, CYP2C8, and CYP3A4	P-gp and BCRP substrate Inhibits P-gp, BCRP, OATP1B1, OATP1B3, and OATP2B1
Ritonavir-boosted paritaprevir-omibitasvir-dasabuvirb	Ritonavir-boosted paritaprevir Hepatic via CYP3A4 (primary) and CYP3A5 Ombitasvir Hydrolysis Dasabuvir Hepatic- via CY2C8 (primary) and CYP2C8	Ritonavir-boosted paritaprevir P-gp, BCRP, OATP1B1, and OATP1B3 substrate Inhibits P-gp, BCRP, UGT1A1, OATP1B1, and OATP1B3 Ombitasvir P-gp and BCRP substrate Inhibits P-gp, BCRP, and UGT1A1 Dasabuvir P-gp and BCRP substrate Inhibits P-gp, BCRP, and UGT1A1
Grazoprevir-elbasvir	Hepatic via CYP3A4 (partial)	Grazoprevir OATP1B1 and OATP1B3 substrate; transported by P-gp Inhibits BCRP (intestinal level), and CYP3A(weak) Elbasvir Inhibits BCRP (intestinal level)
Daclatasvir	Hepatic via CYP3A	CYP3A4 and P-gp substrate Inhibits BCRP, P-gp, OATP1B1, and OATP1B3 (moderate)
Simeprevir	Hepatic via CYP3A (primary), CYP2C8, and CYP2C19	CYP3A4, P-gp, BCRP, OATP1B1, OATP1B3, and OATP2B1 substrate; transported by OATP1B1 and OATP1B3 Inhibits OATP1B1, OATP1B3, P-gp, BCRP, BSEP, CYP1A2 (mild), and CYP3A4 (mild)
Ribavirinc	Hepatic and intracellular	Inhibits CYP1A2 and IMDH

BCRP, breast cancer resistance protein; CYP, cytochrome P450 enzymatic system; IMDH, inosine monophosphate dehydrogenase; OATP, organic anion transporting polypeptide; P-gp, p-glycoprotein.

^aMetabolism and transporter effects do not include sofosbuvir; refer to sofosbuvir for information.

^bRitonavir has no activity against HCV but is given as a low-dose CYP3A inhibitor to boost paritaprevir concentration.

^cRibavirin is often used in combination with DAAs; therefore, it is included to provide a comprehensive overview.