. 2023 May 23;5(1):vdad054. doi: 10.1093/noajnl/vdad054

Table 4.

Key Plasma PK Parameters of Selumetinib and Selumetinib Metabolite (N-desmethyl Selumetinib)

Parameter (Units)	Statistic	Single Dose (Cycle 1 day 1; N = 12)		Steady State (Cycle 2 day 1; n = 11)
Parameter (Units)	Statistic	Selumetinib	N-desmethyl Selumetinib	Selumetinib	N-desmethyl Selumetinib
C_max (ng/mL)	Geometric mean	783.1	55.5	869.4	40.9
C_max (ng/mL)	gCV%	52.7	49.1	53.5	53.1
t_max (h)	Median	1.5	NA	1.5	NA
t_max (h)	Min–Max	0.5–3.1	NA	0.4–2.9	NA
AUC_0–t^a (ng·h/mL)	Geometric mean	2224	169.7	2395	123.6
AUC_0–t^a (ng·h/mL)	gCV%	37.6	35.4	40.3	37.3
AUC_0–6 (ng·h/mL)	Geometric mean	1926	140.8	2396	123.6
AUC_0–6 (ng·h/mL)	gCV%	41.6	38.9	40.3	37.3
AUC_0–12 (ng·h/mL)	Geometric mean	2523^b	188.7^c	NA	NA
AUC_0–12 (ng·h/mL)	gCV%	24.2	24.3	NA	NA
C_trough (ng/mL)	Geometric mean	NA	NA	92.7	6.7
C_trough (ng/mL)	gCV%	NA	NA	63.2	57.1
Rac C_max	Geometric mean	NA	NA	1.10	0.7
Rac C_max	gCV%	NA	NA	34.3	42.2
Rac AUC^d	Geometric mean	NA	NA	1.27	0.9
Rac AUC^d	gCV%	NA	NA	17.3	43.1
Metabolite:parent ratio C_max	Geometric mean	NA	0.07	NA	0.05
Metabolite:parent ratio C_max	gCV%	NA	18.3	NA	62.8
Metabolite:parent ratio AUC^e	Geometric mean	NA	0.08	NA	0.05
Metabolite:parent ratio AUC^e	gCV%	NA	15.9	NA	55.5

^aThe last sample was 10–12 hours post dose for cycle 1 day 1 and 6 hours post dose for cycle 2 day 1.

^b n = 8.

^c n = 7.

^dRac AUC was calculated using AUC_0–6 for cycle 1 day 1 and cycle 2 day 1.

^eMetabolite: Parent ratio for AUC was calculated using AUC_0–t for selumetinib and N-desmethyl selumetinib.

AUC, area under the concentration–time curve; AUC_0–6, AUC from time 0 to 6 hours; AUC_0–12, AUC from time 0 to 12 hours; AUC_0–t, AUC from time 0 to last measurable concentration; C_max, maximum plasma concentration; C_trough, lowest concentration of selumetinib prior to next dose; gCV, geometric coefficient of variation; NA, not applicable; PK, pharmacokinetics; RAC, accumulation ratio; t_max, time to maximum plasma concentration.