Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects

Table 1 Pharmacokinetics parameters of test and reference formulations of esomeprazole under fasting status (pharmacokinetics analysis set)

PK parameters (unit)	mean ± SD (CV%), 1n = 32
	2n	Test formulation	2n	Reference formulation
Cmax (ng/mL)	64	1709.563 ± 650.8205 (38.07%)	64	1635.875 ± 591.2969 (36.15%)
AUC0-t (hr*ng/mL)	64	4328.5196 ± 2109.6280 (48.74%)	64	4132.7124 ± 1991.9727 (48.20%)
AUC0-inf (hr*ng/mL)	64	4395.5223 ± 2173.2633 (49.44%)	64	4187.7795 ± 2046.3196 (48.86%)
Tmax (h)	64	2.000 (1.00, 4.00)	64	2.500 (1.00, 5.00)
%AUCex	64	1.135 ± 1.8793 (165.54%)	64	1.040 ± 1.1709 (112.60%)
λz (1/h)	64	0.5685 ± 0.1969 (34.64%)	64	0.5757 ± 0.1967 (34.16%)
t1/2 (h)	64	1.366 ± 0.4855 (35.53%)	64	1.329 ± 0.3972 (29.89%)
CL/F (L/h)	64	12.3599 ± 8.6012 (69.59%)	64	13.2105 ± 9.5635 (72.39%)
Vd/F (L)	64	20.3287 ± 6.4901 (31.93%)	64	21.3166 ± 8.6636 (40.64%)

T_max is expressed as the median (min, max).

¹n is the pharmacokinetics analysis set population.

²n is the statistical analysis population.

PK: Pharmacokinetics; SD: Standard deviation; AUC: Area under the curve.

Table 2 Pharmacokinetics parameters of test and reference formulations of esomeprazole under fed status (pharmacokinetics analysis set)

PK parameters (unit)	mean ± SD (CV%), 1n = 32
	2n	Test formulation	2n	Control formulation
Cmax (ng/mL)	64	360.373 ± 249.7500 (69.30%)	64	390.725 ± 257.6718 (65.95%)
AUC0-t (hr*ng/mL)	64	1285.9846 ± 965.7697 (75.10%)	64	1363.9129 ± 887.0435 (65.04%)
AUC0-inf (hr*ng/mL)	63	1366.4590 ± 1014.866 (74.27%)	58	1497.9755 ± 979.5204 (65.39%)
Tmax (h)	64	5.000 (2.00, 8.00)	64	5.000 (3.00, 10.00)
%AUCex	63	4.154 ± 6.7878 (163.39%)	58	4.191 ± 5.6377 (134.53%)
λz (1/h)	63	0.5766 ± 0.1851 (32.11%)	58	0.5529 ± 0.1602 (28.98%)
t1/2 (h)	63	1.454 ± 0.9882 (67.97%)	58	1.408 ± 0.5896 (41.89%)
CL/F (L/h)	63	54.4431 ± 60.2376 (110.64%)	58	47.2423 ± 47.5796 (100.71%)
Vd/F (L)	63	101.5421 ± 111.3586 (109.67%)	58	93.9881 ± 113.9048 (121.19%)

T_max is expressed as the median (min, max).

¹n is the pharmacokinetics analysis set population.

²n is the statistical analysis population.

PK: Pharmacokinetics; SD: Standard deviation; AUC: Area under the curve.

Table 3 Bioequivalence analysis of esomeprazole (fasting arm)–primary endpoint pharmacokinetics parameters (bioequivalence analysis set)

	Average bioequivalence					Reference-scaled average bioequivalence				Intra-subject variability (%)
Parameters	n	GLSmean T	GLSmean R	Ratio (%) (T vs R)	90%CI (%)	S2wr	Swr	Point estimate (0.8, 1.25)	Criteria bound (≤ 0)	CVwt	CVwr
Cmax (ng/mL)	32	1591.275	1527.891	104.15	(98.20, 110.46)	0.0427	0.2067	1.0415	-0.0193	15.04	20.89
AUC0-t (h*ng/mL)	32	3786.532	3597.451	105.26	(99.80, 111.01)	0.0484	0.2199	1.0526	-0.0228	18.39	22.26
AUC0-inf (h*ng/mL)	32	3830.746	3635.508	105.37	(99.97, 111.06)	0.0473	0.2175	1.0537	-0.0222	18.31	22.01

AUC: Area under the curve.

Table 4 Bioequivalence analysis of esomeprazole (fed arm) – primary endpoint pharmacokinetics parameters (bioequivalence analysis set)

	Average bioequivalence					Reference-scaled average bioequivalence				Intra-subject variability (%)
Parameters	n	GLSmean T	GLSmean R	Ratio (%) (T vs R)	90%CI (%)	S2wr	Swr	Point estimate (0.8, 1.25)	Criteria bound (≤ 0)	CVwt	CVwr
Cmax(ng/mL)	32	284.060	298.718	95.09	(80.92, 111.75)	0.3238	0.5690	0.9509	-0.1689	53.05	61.84
AUC0-t (h*ng/mL)	32	958.8895	1065.110	90.03	(79.29, 102.22)	0.2281	0.4776	0.9003	-0.1015	39.91	50.62
AUC0-inf (h*ng/mL)	26	1074.615	1271.273	84.53	(72.99, 97.90)	0.2260	0.4754	0.8453	-0.0593	42.76	50.36

AUC: Area under the curve.