Comparison of Bioavailability and Bioequivalence of Generic and Brand Name Formulations of Escitalopram Oxalate Tablets in Healthy Chinese Population Under Fasting and Fed Conditions

Figures & data

Figure 1 Chemical structure of escitalopram oxalate.

Table 1 Demographic Characteristics and Other Baseline Values of Test-Reference Treatment (T-R) and Reference-Test Treatment (R-T) Groups Under Fasting and Fed Conditions

Characteristics	Fasting		Fed
	T-R ^a (n=11)	R-T (n=12)	T-R (n=12)	R-T (n=12)
Sex, no. (%)
Male	8(72.73)	9(75.00)	9(75.00)	9(75.00)
Female	3(27.27)	3(25.00)	3(25.00)	3(25.00)
Nationality, no. (%)
Han	9(81.82)	12(100.00)	11(91.67)	9(75.00)
Other	2(18.18)	0(0.00)	1(8.33)	3(25.00)
Age, years
Mean (SD)	28.00(6.42)	29.83(7.37)	29.33(7.49)	26.25(6.81)
Median	29.00	29.00	28.00	24.00
Range	19.00,40.00	21.00,44.00	20.00,46.00	18.00,44.00
Height, cm
Mean (SD)	168.55(6.01)	167.58(6.27)	174.92(9.00)	168.92(7.14)
Median	169.00	168.00	178.00	169.50
Range	158.00,178.00	156.00,176.00	158.00,185.00	156.00,181.00
Body weight, kg
Mean (SD)	63.55(7.47)	62.50(8.26)	70.92(9.57)	65.25(8.60)
Median	65.00	61.50	73.00	63.50
Range	53.00,74.00	50.00,79.00	53.00,83.00	55.00,84.00
BMI, kg/m^2
Mean (SD)	22.33(1.88)	22.20(2.09)	23.11(2.05)	22.89(2.81)
Median	22.28	22.33	22.47	23.19
Range	19.13,25.31	19.29,25.50	19.75,25.83	19.26,25.97

Note: ^aOne subject withdrew consent due to personal reasons without medication.

Table 2 The Main Pharmacokinetic Parameters After Oral Administration of 20 Mg Escitalopram Oxalate Tablets Under Fasting and Fed Conditions

Parameter ^a	Fasting (n = 21)		Fed (n = 19)
	Test	Reference	Test	Reference
Cmax (ng/mL)	29.1 (6.6)	26.7 (4.5)	24.3 (4.6)	22.7 (3.3)
AUC0-t (h.ng/mL)	1020.20 (348.85)	1004.15 (339.43)	1044.16 (384.28)	975.09 (365.80)
AUC0-∞ (h.ng/mL)	1088.61 (433.87)	1072.63 (421.51)	1136.31 (521.70)	1067.36 (489.39)
λZ (h^−1)	0.02 (0.005)	0.019 (0.005)	0.02 (0.007)	0.02 (0.007)
t1/2 (h)	37.26 (10.48)	38.36 (10.33)	38.95 (14.52)	39.81 (14.92)
tmax (h) ^b	2.0 (1.5, 4.5)	2.0 (1.5, 3.0)	4.5 (1.5, 8.0)	4.0 (1.5, 5.0)
F (%)	101.83(9.79)		107.95 (10.91)

Notes: ^aValues expressed as mean (standard deviation); ^bValues expressed as median (range).

Abbreviations: C_max, the highest plasma concentration of the drug; T_max, the time to arrive C_max; λ_z, the elimination rate constant; t_1/2, the elimination half-life; AUC_0–t, the area under the plasma concentration–time curve from time zero to the last quantifiable concentration time; AUC_0-∞, the area under the plasma concentration–time curve from time zero extrapolated to infinite time; F, relative bioavailability.

Table 3 Statistical Comparison After Ln-Transformed C_max, AUC_0-t and AUC_0-∞of the Test and Reference Formulations Under Fasting Conditions (n = 21)

Parameter	Geometric Mean		Geometric Mean Ratio (%)	90% CI (%)	CV (%)	Power (%)
	Test	Reference
Cmax (ng/mL)	28.4	26.4	107.74	102.87, 112.85	8.69	100
AUC0-t (h.ng/mL)	966.79	953.23	101.42	97.85, 105.12	6.72	100
AUC0-∞ (h.ng/mL)	1018.02	1005.01	101.29	97.51, 105.23	7.15	100

Abbreviations: C_max, the highest plasma concentration of the drug; AUC_0–t, the area under the plasma concentration–time curve from time zero to the last quantifiable concentration time; AUC_0-∞, the area under the plasma concentration–time curve from time zero extrapolated to infinite time.

Table 4 Statistical Comparison After Ln-Transformed C_max, AUC_0-t and AUC_0-∞ of the Test and Reference Formulations Under Fed Conditions (n = 19)

Parameter	Geometric Mean		Geometric Mean Ratio (%)	90% CI (%)	CV (%)	Power (%)
	Test	Reference
Cmax (ng/mL)	24.0	22.4	106.84	102.17, 111.71	7.91	100
AUC0-t (h.ng/mL)	986.03	918.59	107.34	103.25, 111.60	6.89	100
AUC0-∞ (h.ng/mL)	1048.97	983.00	106.71	102.67, 111.92	6.85	100

Abbreviations: C_max, the highest plasma concentration of the drug; AUC_0–t, the area under the plasma concentration–time curve from time zero to the last quantifiable concentration time; AUC_0-∞, the area under the plasma concentration–time curve from time zero extrapolated to infinite time.

Table 5 ANOVA Test After Ln-Transformed C_max, AUC_0-t and AUC_0-∞ of the Test and Reference Formulations Under Fasting and Fed Conditions

Parameter	Factor	Fasting	Fed
Ln Cmax	Sequence	0.963	0.475
	Subjects	<0.001	<0.001
	Period	0.9 48	0.097
Ln AUC0-t	Sequence	0.488	0.932
	Subjects	<0.001	<0.001
	Period	0.894	0.378
Ln AUC0-∞	Sequence	0.472	0.885
	Subjects	<0.001	<0.001
	Period	0.894	0.332

Abbreviations: ANOVA, analysis of variance; C_max, the highest plasma concentration of the drug; AUC_0–t, the area under the plasma concentration–time curve from time zero to the last quantifiable concentration time; AUC_0-∞, the area under the plasma concentration–time curve from time zero extrapolated to infinite time.

Figure 2 Mean plasma concentration-time profiles after oral administration of 20 mg escitalopram oxalate tablets of the test and reference formulations under fasting conditions.

Notes: Error bars represent standard deviation. There were 23 subjects for the test formulation and 22 subjects for the reference formulation.

Figure 3 Mean plasma concentration-time profiles after oral administration of 20 mg escitalopram oxalate tablets of the test and reference formulations under fed conditions.

Notes: Error bars represent standard deviation. There were 24 subjects for the test formulation and 22 subjects for the reference formulation.

Table 6 The Incidence Rate and Comparison of AEs for the Two Formulations Under Fasting and Fed Conditions

	Fasting				Fed
	Test (n=23)		Reference (n=22)		Test (n=24)		Reference (n=22)
	Case	Subject No. (%)	Case	Subject No. (%)	Case	Subject No. (%)	Case	Subject No. (%)
AEs	14	6 (26.09)	12	6 (27.27)	7	7 (29.17)	5	4 (18.18)
ADR	9	4 (17.39)	6	5 (22.73)	6	6 (25.00)	5	4 (18.18)
SAEs	0	0 (0.00)	0	0 (0.00)	0	0 (0.00)	0	0 (0.00)
SADR	0	0 (0.00)	0	0 (0.00)	0	0 (0.00)	0	0 (0.00)
AEs leading to dropout	1	1 (4.35)	0	0 (0.00)	2	2 (8.33)	0	0 (0.00)
ADR leading to dropout	1	1 (4.35)	0	0 (0.00)	2	2 (8.33)	0	0 (0.00)

Abbreviations: AEs, adverse events; ADR, adverse drug reaction; SAEs, serious adverse events; SADR, serious adverse drug reaction.

Table 7 Summary of AEs for the Test and Reference Formulations Under Fasting and Fed Conditions

	Test		Reference
	Case	Subject No. (%)	Case	Subject No. (%)
Fasting^a
Positive urine erythrocyte	3	1 (4.35)	0	0
Increased blood bilirubin	1	1 (4.35)	1	1 (4.55)
Decreased white blood cell count	1	1 (4.35)	0	0
Increased white blood cell count	0	0	1	1 (4.55)
Increased amylase	1	1 (4.35)	0	0
Prolonged APTT	0	0	1	1 (4.55)
Increased direct bilirubin	1	1 (4.35)	0	0
Increased lymphocyte percentage	0	0	1	1 (4.55)
Increased lymphocyte count	0	0	1	1 (4.55)
Increased blood lactate dehydrogenase	1	1 (4.35)	0	0
Decreased neutrophil percentage	0	0	1	1 (4.55)
Decreased neutrophil count	1	1 (4.35)	0	0
Nausea	3	3 (13.04)	3	3 (13.64)
Diarrhea	0	0	1	1 (4.55)
Vomiting	1	1 (4.35)	0	0
Upper respiratory tract viral infection	1	1 (4.35)	2	2 (9.09)
Fed^b
Drowsiness	2	2 (8.33)	1	1 (4.55)
Sleepiness	1	1 (4.17)	1	1 (4.55)
Nausea	1	1 (4.17)	1	1 (4.55)
Vomiting	2	2 (8.33)	0	0
Decreased red blood cell count	0	0	1	1 (4.55)
Increased blood bilirubin	0	0	1	1 (4.55)
Increased blood uric acid	1	1 (4.17)	0	0

Notes: ^a23 subjects entered the Safety Set (SS) for test formulation and 22 subjects entered the SS for reference formulation under fasting condition; ^b24 subjects entered the SS for test formulation and 22 subjects entered the SS for reference formulation under fed condition.

Abbreviation: APTT, activated partial thromboplastin time.