. 2017 Apr 21;11:1283–1290. doi: 10.2147/DDDT.S133814

Table 1.

Kinetic parameters for O-desmethyl gefitinib activities of recombinant wild-type and 24 mutant CYP2D6 proteins against gefitinib

Variants	Allele frequency (%)	V_max (pmol/min/pmol P450)	K_m (μM)	K_si (μM)	Clint (V_max/K_m)	Relative clearance (% of wild type)
CYP2D6.1	26.56	1.25±0.02	6.94±0.44	158.10±31.16	0.18±0.01	100.00
CYP2D6.2 (R296C; S486T)	10.34	0.82±0.14	19.61±4.69^**	31.61±6.97^**	0.04±0.00^**	23.43^**
CYP2D6.10 (P34S; S486T)	42.86	0.09±0.00^**	16.83±1.53^*	41.86±1.73^**	0.01±0.00^**	3.11^**
CYP2D6.87 (A5V)	0.023	1.31±0.03	11.02±0.42	62.21±4.16^**	0.12±0.00^**	65.82^**
CYP2D6.88 (V104A)	0.094	2.28±0.21^**	11.80±1.70	93.66±15.33^**	0.19±0.01	107.23
CYP2D6.89 (L142S)	0.023	2.06±0.06^**	12.65±0.63	40.98±2.76^**	0.16±0.00	90.21
CYP2D6.90 (K147R)	0.047	1.83±0.08^*	15.17±0.40	74.55±6.36^**	0.12±0.00^**	66.97^**
CYP2D6.91 (C161S)	0.023	1.85±0.08^**	12.42±0.69	75.72±6.97^**	0.15±0.00	82.68
CYP2D6.92 (218frameshift)	0.023	ND	ND	ND	ND	ND
CYP2D6.93 (T249P)	0.023	0.07±0.00^**	10.61±0.43	88.43±15.92^**	0.01±0.00^**	3.68^**
CYP2D6.94 (D337G)	0.164	1.46±0.22	4.57±1.62	113.04±42.64^**	0.34±0.07^**	184.78^**
CYP2D6.95 (R388H)	0.047	1.27±0.02	14.46±0.59	88.79±2.62^**	0.09±0.00^**	48.82^**
CYP2D6.96 (424STOP)	0.074	ND	ND	ND	ND	ND
CYP2D6.97 (F457L)	0.047	1.42±0.04	8.32±0.62	58.58±2.45^**	0.17±0.01	94.72
CYP2D6.98 (H463D)	0.023	7.86±0.37^**	96.63±5.08^**	5.92±0.30^**	0.08±0.00^**	45.13^**
R25Q	0.023	1.31±0.48	23.67±11.93^**	13.79±5.10^**	0.06±0.01^**	32.30^**
F164L	0.023	1.68±0.10	11.45±0.69	74.59±8.44^**	0.15±0.00	81.30
E215K	0.047	0.69±0.07^*	39.32±5.27^**	14.46±1.78^**	0.02±0.00^**	9.79^**
F219S	0.023	1.29±0.05	7.71±0.28	83.21±12.52^**	0.17±0.00	93.16
V327M	0.023	0.94±0.14	9.00±2.54	67.10±13.51^**	0.11±0.01^**	58.91^**
D336N	0.023	2.93±0.40^**	24.08±4.91^**	20.31±3.49^**	0.12±0.01^**	67.81^**
V342M	0.023	2.99±0.24^**	13.71±1.29	29.59±3.42^**	0.22±0.00	120.96
R344Q	0.023	2.28±0.02^**	15.92±0.29^*	28.90±0.55^**	0.14±0.00	79.35
R440C	0.023	1.86±0.31^**	19.93±4.21^**	11.56±2.80^**	0.09±0.00^**	52.07^**
R497C	0.023	1.21±0.14	9.76±2.04	77.45±18.65^**	0.13±0.01^**	69.42^**

Notes: Data are presented as the mean ± standard deviation of three parallel experiments. Significantly different from the wild-type,

P<0.05 and

^**

P<0.01.

Abbreviations: CYP2D6, cytochrome P450 2D6; K_m, Michaelis constant; V_max, maximum initial velocity of the enzyme; K_si, substrate inhibition constant; C_lint, intrinsic clearance; ND, not determined.