Table 3.

Metoprolol and α-hydroxymetoprolol PK parameters (mean ± SD) in patients with CML after a single 100 mg dose metoprolol alone (day 1) and in combination with imatinib (day 8) (n = 20)

Analyte	Day	Phenotype	Cmax (ng ml−1)	tmax (h)	AUC (0,∝) (ng ml−1 h)	t½ (h)	CL/F (l h−1)	MR
Metoprolol	1	IMs (n = 6)	177 ± 55.9	2 (1, 4)	1190 ± 365	4.8 ± 0.5	95 ± 44	0.53 ± 0.37
		EMs (n = 13)	131 ± 49.2	2 (1.5, 3)	660 ± 337	3.6 ± 1.0	175 ± 59	1.32 ± 0.62
		NA (n = 1)	76.7	2	462	3.6	216	1.23
		Data pooled (n = 20)	142.2 ± 55.2	2 (1, 4)	811 ± 418	3.9 ± 1.0	153 ± 66	1.08 ± 0.65
	8	IMs (n = 6)	204 ± 54.5	2.5 (1.5, 3.1)	1390 ± 376	4.9 ± 0.7	78 ± 227	0.60 ± 0.36
		EMs (n = 13)	159 ± 48.3	2 (1.5, 4)	818 ± 397	3.7 ± 1.1	141 ± 48	1.36 ± 0.62
		NA (n = 1)	152	1.5	591	3.8	169	1.46
		Data pooled (n = 20)	171.9 ± 52.0	2 (1.5, 4)	979 ± 465	4.1 ± 1.1	123 ± 51	1.14 ± 0.64
α-hydroxy-metoprolol	1	IMs (n = 6)	33.6 ± 10.7	3.5 (1.5, 5)	531 ± 109	9.8 ± 1.1
		EMs (n = 13)	56.5 ± 19.2	2 (1.5, 3)	729 ± 143	8.9 ± 1.1
		NA (n = 1)	53.7	5	569	7.3
		Data pooled (n = 20)	49.5 ± 19.4	3 (1.5, 5)	662 ± 158	9.1 ± 1.7
	8	IMs (n = 6)	32.1 ± 7.6	4.1 (3, 8)	751 ± 209	10.2 ± 2.0
		EMs (n = 13)	49.5 ± 15.1	3 (2, 5)	946 ± 174	10.3 ± 2.1
		NA (n = 1)	64	3	865	9.2
		Data pooled (n = 20)	45.0 ± 15.6	3 (2, 8)	883 ± 197	10.2 ± 1.9

IMs, intermediate metabolizers; EMs, extensive metabolizers; NA, unknown CYP2D6 status; MR, metabolic to parent drug AUC ratio. C_max, maximum observed concentration; t_max, time to reach C_max (t_max presented as median and range); AUC(0,∝), area under the plasma concentration–time curve from time 0 to infinity; t_1/2, elimination half-life; CL/F, oral clearance; MR, metabolic ratio calculated as the AUC(0,∝) ratio of α-hydroxymetoprolo to metoprolol