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. 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)
Selumetinib N-desmethyl Selumetinib Selumetinib N-desmethyl Selumetinib
Cmax (ng/mL) Geometric mean 783.1 55.5 869.4 40.9
gCV% 52.7 49.1 53.5 53.1
tmax (h) Median 1.5 NA 1.5 NA
Min–Max 0.5–3.1 NA 0.4–2.9 NA
AUC0–ta (ng·h/mL) Geometric mean 2224 169.7 2395 123.6
gCV% 37.6 35.4 40.3 37.3
AUC0–6 (ng·h/mL) Geometric mean 1926 140.8 2396 123.6
gCV% 41.6 38.9 40.3 37.3
AUC0–12 (ng·h/mL) Geometric mean 2523b 188.7c NA NA
gCV% 24.2 24.3 NA NA
Ctrough (ng/mL) Geometric mean NA NA 92.7 6.7
gCV% NA NA 63.2 57.1
Rac Cmax Geometric mean NA NA 1.10 0.7
gCV% NA NA 34.3 42.2
Rac AUCd Geometric mean NA NA 1.27 0.9
gCV% NA NA 17.3 43.1
Metabolite:parent ratio Cmax Geometric mean NA 0.07 NA 0.05
gCV% NA 18.3 NA 62.8
Metabolite:parent ratio AUCe Geometric mean NA 0.08 NA 0.05
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 AUC0–6 for cycle 1 day 1 and cycle 2 day 1.

eMetabolite: Parent ratio for AUC was calculated using AUC0–t for selumetinib and N-desmethyl selumetinib.

AUC, area under the concentration–time curve; AUC0–6, AUC from time 0 to 6 hours; AUC0–12, AUC from time 0 to 12 hours; AUC0–t, AUC from time 0 to last measurable concentration; Cmax, maximum plasma concentration; Ctrough, lowest concentration of selumetinib prior to next dose; gCV, geometric coefficient of variation; NA, not applicable; PK, pharmacokinetics; RAC, accumulation ratio; tmax, time to maximum plasma concentration.