Drug–drug interaction study of imatinib and voriconazole in vitro and in vivo

Figures & data

Figure 1 The effect of 100 μM VOR on IMA metabolite (CGP74588) formation (A) and various concentrations (0, 0.01, 0.1, 1, 10, 50, 100, and 1,000 μM) of VOR for IC₅₀ (B) in RLMs. Values are Mean ± SD, n=3.

Figure 2 The effect of 100 μM IMA on VOR metabolite (N-oxide VOR) formation (A) and various concentrations (0, 0.01, 0.1, 1, 10, 20, 50, and 100 μM) of IMA for IC₅₀ (B) in RLMs. Values are Mean ± SD, n=3. *P<0.05.

Table 1 Pharmacokinetic parameters of IMA, VOR, and their metabolites in three different groups (n=8)

Parameters	IMA		CGP74588		VOR		N-oxide VOR
	Group A	Group C	Group A	Group C	Group B	Group C	Group B	Group C
AUC0→t (µg/mL•h)	38.37±6.33	43.52±8.65	4.42±0.51	3.38±0.60**	30.47±8.52	59.76±5.36***	31.42±6.80	18.49±6.05**
AUC0→∞ (µg/mL•h)	38.89±6.31	44.01±8.74	4.71±0.71	3.53±0.61**	30.81±8.21	59.87±5.37***	32.74±6.91	19.77±6.37**
MRT0→t (h)	9.43±0.43	9.34±0.61	10.93±1.09	10.83±0.87	6.65±0.89	7.83±0.25*	11.20±1.28	10.62±1.68
MRT0→∞ (h)	9.91±0.45	9.75±0.82	11.16±1.25	11.58±0.88	6.69±0.96	7.91±0.24*	11.37±1.25	10.94±1.74
t1/2 (h)	5.39±0.85	5.14±0.74	8.30±1.27	7.34±1.54	3.31±0.53	3.66±0.45	8.67±0.49	7.24±0.37
Tmax (h)	3.86±0.69	5.00±0.82	3.71±0.56	5.00±1.10	1.64±0.24	2.86±0.28*	7.43±0.98	6.00±0.63
CL (L/h)	0.52±0.04	0.47±0.07	4.33±0.60	5.80±0.90**	0.69±0.17	0.34±0.03**	1.12±0.24	1.33±0.27
Cmax (µg/mL)	2.77±0.22	3.29±0.55*	0.34±0.07	0.24±0.05*	3.08±0.26	4.42±0.20***	2.38±0.45	1.88±0.41*

Notes: Compared to the control group, *P<0.05, **P<0.01, ***P<0.001.

Figure 3 Mean plasma concentration versus time of IMA (A), CGP74588 (B), VOR (C), N-oxide VOR (D) in three group rats (Mean ± SD, n=8).