Table 2

Summary of input parameters for perpetrator drugs used in the mechanistic model-based predictions of transporter- and cytochrome P450–based drug-drug interactions

Perpetrator Drug	K_a	F_a	F_g	Plasma f_u	R_b	f_u,gut	Interaction Potential
	min⁻¹
Cyclosporine	0.025	0.86	0.48	0.068	1.36	1	Reversible inhibition of OATP1B1 (K_i = 0.014 µM), CYP3A4 (K_i = 2 µM), MRP2 (K_i = 4.1 µM) and BCRP (K_i = 6.7 µM)
Gemfibrozil	0.05	1	1	0.03	0.82	1	Reversible inhibition of OATP1B1 (K_i = 2.54 µM) and OAT3 (K_i = 3.4 µM)
Gemfibrozil-1-O-β-glucuronide				0.115	1.0		Reversible inhibition of OATP1B1 (K_i = 7.9 µM) and OAT3 (K_i = 9.9 µM); time-dependent inhibition of CYP2C8 (K_I = 10.1 µM, K_inact = 12.6/h)
Rifampicin	0.0085	1	0.99	0.15	0.9	0.15	Reversible inhibition of OATP1B1 (K_i = 0.5 µM); induction of CYP3A4 (E_max = 49.5, EC₅₀ = 0.23 µM)
Clarithromycin	0.04	1	0.69	0.18	1.0	1	Reversible inhibition of OATP1B1 (K_i = 8.3 µM); time-dependent inhibition of CYP3A4 (K_I = 14 µM, K_inact = 1.7/h)
Itraconazole	0.01	0.85	0.83	0.036	0.58	0.016	Reversible inhibition of CYP3A4 (K_i = 0.0013 µM)
4-OH-Itraconazole				0.021	1.0		Reversible inhibition of CYP3A4 (K_i = 0.014 µM)

F_a, fraction of drug absorbed; F_g, fraction of drug escaping gut-wall extraction; f_u, fraction unbound; f_u_,_gut, fraction unbound in the gut; K_a, absorption rate constant; R_b, blood-to-plasma ratio.