Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

Figures & data

Figure 1 Study design.

Note: *Ending with the morning dose on day 9.
Abbreviations: bid, twice daily; PK, pharmacokinetic.

Table 1 Baseline demographics

	Apixaban (n=12)	Placebo (n=6)
Sex, n (%)
Male	8 (67)	4 (67)
Female	4 (33)	2 (33)
Age, years
Mean (SD)	35 (3)	32 (4)
Range	32–39	28–38
Race, n (%)
Asian	12 (100)	6 (100)
Body weight, kg
Mean (SD)	63.1 (5.0)	61.4 (7.3)
Range	54.0–68.0	54.0–72.0
Height, cm
Mean (SD)	163.7 (5.3)	166.2 (6.0)
Range	152.0–169.0	156.0–174.5
BMI, kg/m^2
Mean (SD)	23.5 (0.7)	22.2 (1.6)
Range	21.4–24.0	19.5–23.6

Abbreviations: BMI, body mass index; SD, standard deviation.

Figure 2 Mean plasma apixaban concentration versus time (n=12) following single-dose administration (day 1) and at steady state (day 9). Error bars show +1 standard deviation from the mean.

Table 2 Summary statistics of single- and multiple-dose apixaban pharmacokinetic parameters (n=12)

	Cmax, ng/mL Geom mean (CV%)	Tmax, hours Median (min, max)	AUC0–t, ng*hour/mL Geom mean (CV%)	AUC∞, ng*hour/mL Geom mean (CV%)	t½, hours Mean (SD)	CLR, L/hour Mean (SD)
Single dose	233.9 (26)	3 (2, 4)	2,273 (27)	2,308 (27)	11.4 (3.6)	1.17 (0.2)
	Cmax, ng/mL	Tmax, hours	Cmin, ng/mL	AUCτ, ng*hour/mL	t½, hours	CLR, L/hour	AI
	Geom mean (CV%)	Median (min, max)	Geom mean (CV%)	Geom mean (CV%)	Mean (SD)	Mean (SD)	Geom mean (CV%)
Multiple doses	336.3 (24)	3.5 (2, 4)	116 (30)	2,703 (24)	10.8 (4.9)	1.20 (0.26)	1.69 (17)

Abbreviations: Al, accumulation index; AUC_0–t, area under plasma concentration curve from time 0 to time of last quantifiable concentration following a single dose; AUC_∞, area under plasma concentration curve from time 0 extrapolated to time infinity; AUC_τ, area under plasma concentration curve in one dosing interval; CL_R, renal clearance; C_max, maximum observed plasma concentration; C_min, minimum observed plasma concentration; CV, coefficient of variation; Geom, geometric; min, minimum; max, maximum; t_1/2, plasma half-life; T_max, time to maximum observed plasma concentration.

Figure 3 Mean anti-Xa activity and plasma apixaban concentration versus time following single-dose administration (day 1) and at steady state (day 9). Error bars show +1 standard deviation from the mean.

Figure 4 Scatter plot of anti-Xa activity versus plasma apixaban concentration. Anti-Xa activity values less than lower limit of quantitation are excluded.

Note: Regression equation: Anti-Xa =0.01690+0.09597 × concentration.