TABLE 7

Comparison of PK parameters between simulated and observed data for model verification of the mechanistic kidney model of rivaroxaban after a 20 mg single dose in healthy subjects

Healthy controls are defined as having creatinine clearance > 80 ml/min.

PK Parameter	Single Dose (20 mg)
	Simulated (n = 130)			Observed (n = 13)
	AUC	C_max	CL_R	AUC	C_max	CL_R
	µg⋅h/l	µg/l	l/h	µg⋅h/l	µg/l	l/h
Healthy, P-gp only^{^a}
Geometric mean	3901	311	0.37	2583	263	2.42
CV (%)	52	31	27	21	26	23
Ratio of simulated/observed	1.51	1.18	0.15
Success criteria for ratio of simulated/observed	0.78–1.29	0.74–1.35	0.76–1.31
Healthy, OAT3 only^{^a}
Geometric mean	2946	269	1.60	2583	263	2.42
CV (%)	45	30	46	21	26	23
Ratio of simulated/observed	1.14	1.02	0.66
Success criteria for ratio of simulated/observed	0.78–1.29	0.74–1.35	0.76–1.31
Healthy, P-gp, and OAT3^{^a}
Geometric mean	2563	263	2.70	2583	263	2.42
CV (%)	43	30	49	21	26	23
Ratio of simulated/observed	0.99	1	1.12
Success criteria for ratio of simulated/observed	0.78–1.29	0.74–1.35	0.76–1.31

CI, confidence interval; CV, coefficient of variation.
↵^a Greenblatt et al. (2018).