Table 3.

Pharmacokinetics of Boceprevir, Telaprevir, Simeprevir, Asunaprevir, Paritaprevir, Grazoprevir, Daclatasvir, Ledipasvir, Ombitasvir, Sofosbuvir and Dasabuvir, which predispose them to drug-drug interactions

Class drug	Absorption	Distribution	Metabolism		Elimination
					mainly
NS3/4A Protease			substrate for	inhibitor or inducer
Inhibitors
First-Wave	↑ by food	PPB 75%	CYP3A4/5	Moderate CYP3A	Hepatic
Boceprevir		P-gp inhibitor	AKR	inhibitor
Telaprevir	↑ by fatty	PPB 60-76%	CYP3A4/5	Strong CYP3A	Hepatic
		Moderate P-gp inhibitor		inhibitor
Second-Wave	↑ by food	PPB 99%	CYP3A4	mildly nhibits	Hepatic
Simeprevir		inhibitor of P-gp, OATP1B1 and		intestinal CYP3A4 and
		MRP2		CYP1A2
Asunaprevir	↑ by fatty meals	PPB 99%	CYP3A	Moderate inhibitor	Hepatic
		inhibitor of P-gp and OATP1B1		of CYP2D6; weak
				inducer of CYP3A4
Paritaprevir	↑ by food	PPB 97-98-%	CYP3A4/5	ND	Hepatic
		substrate for P-gp and BCRP;
		inhibitor of OATP1B1
Grazoprevir		PPB 98.8%	CYP3A	Weak inhibitor of	Hepatic
	↑ by fatty meals	Transported by OATP1B1, P-gp.		CYP3A
		Inhibits BCRP
NS5A Inhibitors
Daclatasvir	↓ by fatty meals	PPB 99%	CYP3A	ND	Hepatic
		inhibitor of P-gp
		and OATP1B1
Ledipasvir	↓ by increasing gastric	PPB 99%	Minimally	ND	as parent drug
	pH	substrate and an inhibitor of P-gp	metabolized
Ombitasvir	↑ by food	PPB 99%	Amide hydrolysis	ND	Hepatic
		substrate of P-gp and BCRP
Elbasvir	↓ by fatty meals	PPB 99.9%	CYP3A	ND	Hepatic
		Transported by, P-gp. Inhibits
		BCRP, P-gp
Velpatasvir	↓ by fatty meals	PPB 99.5%	CYP2B6,		Hepatic
		Transported by and inhibits	CYP2C8,
		P-gp, BCRP, OATP1B1,	CYP3A4
		OATP1B3
NS5B Polymerase Inhibitors
Nucleoside Inhibitors
Sofosbuvir	Food ↔	PPB 61-65%	Prodrug is	ND	Renal
		Substrate of P-gp and BCRP	phosphorylated
			to active-form
Non-Nucleoside Inhibitors
Dasabuvir	↑ by food	PPB 99%	CYP2C8	ND	Hepatic
		substrate of P-gp and BCRP	CYP3A, CYP2D6

AKR: aldo keto reductase; BCRP: breast cancer resistance protein; CYP: cytochrome P450; DAA: direct-acting antiviral agent; MRP: multidrug resistant protein; ND: no data; OATP: organic anion transporting polypeptide; P-gp: P-glycoprotein; PPB: plasma protein binding. ↑ increase; ↓ decrease; ↔ nil