. 2015 May 22;79(6):946–958. doi: 10.1111/bcp.12563

Table 1.

Summary of oncology agents studied as perpetrators of CYP3A-mediated DDI

Drug	Route of administration	CYP3A K_I (μ m)	CYP3A kinact (min⁻¹)	CYP3A K_i (μ m)	CYP3A mRNA E_max	CYP3A mRNA EC₅₀ (μ m)	R1/R2 value for inhibition (systemic C_max)^*	R1/R2 value for inhibition (dose/250 ml)^†	R3 value for induction	Observed AUCR	Clinical probe substrate
abiraterone	orally as acetate prodrug			8.01			1.08	1428
aprepitant	orally			10	6.76	1.81	1.3	95	0.19	3.3	midazolam
axitinib	orally			8.3			1.01	7.2
bicalutamide	orally			2.33			1.77	201		1.9	midazolam
cabazitaxel	i.v.			1.99			1.09	n/a
carfilzomib	i.v.	11	0.1	0.85			7.92	n/a		0.9	midazolam
crizotinib	orally	3	0.11	3.65	19.5	1.45	1.25	610	0.12	3.7	midazolam
dabrafenib	orally			7.89	30	12	1.36	147	0.15	0.26	midazolam
dasatinib	orally	1.9	0.022	18			1.01	33		1.2	simvastatin
enzalutamide	orally			42		^‡	1.74	34		0.12	midazolam
erlotinib	orally	8.2	0.057				44.62	178		0.76	midazolam
everolimus	orally	0.9	0.022	2.3			5.48	19
fosaprepitant	i.v.	^§						n/a		1.6	midazolam
fulvestrant	i.m.			6600			<1.1	n/a		1.11	midazolam
gefitinib	orally	14.1	0.019				4.10	60		n.f.
imatinib	orally	4.4	0.028	8			1.66	407		3.5	simvastatin
ixabepilone	i.v.	7.5	0.043	7.5			9.37	n/a		n.f.
lapatinib	orally	29.2	0.031	1.1			6.00	7825		1.45	midazolam
nilotinib	orally	1.5	0.033	0.448	72		10.6	5064	>4-fold threshold	1.3^¶	midazolam
pazopanib	orally	2.9	0.021	6.25			140.25	1170		1.32	midazolam
romidepsin	i.v.			25.7			1.04	n/a
sirolimus	orally	0.9	0.027	2			2.47	34		1.5	verapamil
sorafenib	orally	0.881	0.045	27.6			1.60	126		0.85	midazolam
sunitinib	orally	31.5	0.02				1.20	60
temsirolimus	i.v.	0.6	0.021	3.1			1.19	n/a		^**
toremifene	orally			8.6		^††	1.23	70		1.0	midazolam
trametinib	orally				37.3	2.7	n/a	n/a	0.65	1.16	everolimus
vemurafenib	orally			>50		^‡‡	n.d.	n.d.		0.61	midazolam

Data obtained from drug label information and CDER Clinical Pharmacology reviews from the drug approval history as listed on http://www.accessdata.fda.gov, supplemented, where needed, with data from literature reports 8,9,14,15.

Threshold based on FDA guidance is R > 1.1. R value was calculated based on reversible inhibition data, followed by TDI data if reversible inhibition R ≤ 1.1.

^†

Threshold based on FDA guidance is R > 11. R value was calculated based on reversible inhibition data, followed by TDI data if reversible inhibition R ≤ 11.

^‡

Concentration dependent effects up to 2.5 μm; < 28% 10 μm rifampin response.

^§

Unstable in human in vitro test systems.

^¶

Following single dose administration of nilotinib.

^**

Not performed, as no in vivo effect of CYP2D6 inhibition was observed.

^††

15% of positive control response at 5 μm.

^‡‡

40% of positive control response. n/a; not applicable.