The Effect Of Food On The Pharmacokinetic Properties And Bioequivalence Of Two Formulations Of Levocetirizine Dihydrochloride In Healthy Chinese Volunteers

Figures & data

Table 1 Demographic Characteristics Of Volunteers In The Fasting And Fed Studies (Mean ± SD [Range])

Parameters	Fasting Study (n=24)	Fed Study (n=25)
Sex, male/female	18/6	19/6
Age, years, mean ± SD [range]	24.25 ± 3.91 [18–35]	23.48 ± 1.73 [19–26]
Weight, kg, mean ± SD [range]	62.40 ± 6.40 [52.1–76.5]	62.34 ± 8.01 [49.9–83.6]
Height, cm, mean ± SD [range]	169.92 ± 5.93 [160–179.5]	170.42 ± 6.77 [161.5–189]
BMI, kg/m^2, mean ± SD [range]	21.58 ± 1.50 [19.6–25]	21.38 ± 1.62 [19.1–24.1]
12-lead electrocardiography, n (%)
Normal	22 (91.67)	17 (68.0)
Abnormally, no clinical significance	2 (8.33)	8 (32.0)
Abnormally, the clinical significance	0	0
X-ray chest, n (%)
Normal	21 (87.5)	25 (100)
Abnormally, no clinical significance	3 (12.5)	0
Abnormally, the clinical significance	0	0

Abbreviation: BMI, body mass index.

Figure 1 Study participation chart. (A) Fasting group; (B) Fed group.

Table 2 Main Pharmacokinetic Parameters For The Generic And Branded Formulations In Fasting And Fed Volunteers

Parameters	Fasting Condition (n=22) Arithmetic Mean ± SD(%CV)		Fed Condition (n=24) Arithmetic Mean ± SD(%CV)
	Generic Formulation	Branded Formulation	Generic Formulation	Branded Formulation
^aTmax (h)	0.75 (0.33, 1.25)	0.75 (0.33, 1.50)	1.38 (0.25, 3.50)**	1.63 (0.50, 4.00)^##
Cmax (ng/mL)	219.23±29.05 (13.25)	219.09±36.78(16.79)	154.13±20.89(13.56)**	145.67±30.61(21.02)^##
AUC0–36h (h·ng/mL)	1,737.88±290.85(16.74)	1,750.33±315.88(18.05)	1,501.58±263.24(17.53)*	1,482.16±265.66(17.92)^#
AUC0-∞(h·ng/mL)	1,808.71±337.99(18.69)	1,819.22±358.46(19.70)	1,559.76±287.15(18.41)*	1,542.97±294.92(19.11)^#
λz (h^−1)	0.095±0.017(17.69)	0.095±0.015(15.72)	0.095±0.013(14.18)	0.094±0.015(15.46)
t1/2 (h)	7.50±1.37(18.19)	7.48±1.20(15.98)	7.47±1.01(13.57)	7.50±1.11(14.82)

Notes: ^aTmax is expressed in median (minimum, maximum). *P<0.05, **P<0.01 for the generic formulation of levocetirizine under fed condition versus that under fasting condition. ^#p<0.05, ^##p<0.01 for the branded formulation of levocetirizine under fed condition versus that under fasting condition.

Table 3 Geometric Mean, Ratio, Intra-Individual Variability, And 90% Confidence Intervals For Levocetirizine In Fasting And Fed Conditions

Parameters	Fasting Condition (n=22)					Fed Condition (n=23)
	Geometric Mean and Ratio			Intra-Individual Variability (%CV)	90% CIs	Geometric Mean and Ratio			Intra-Individual Variability (%CV)	90% CIs
	Generic Formulation	Branded Formulation	(Generic/Branded)%			Generic Formulation	Branded Formulation	(Generic/Branded)%
Cmax (ng/mL)	217.229	215.503	100.8	11.90	94.75–107.24	152.178**	142.110^##	107.1	13.58%	99.98–114.69
AUC0–36h (h·ng/mL)	1,717.378	1,722.742	99.7	4.90	97.17–102.27	1,486.410*	1,467.359^#	101.3	5.11%	98.71–103.96
AUC0-∞ (h·ng/mL)	1,782.428	1,786.390	99.8	5.16	97.13–102.50	1,541.563*	1,524.338^#	101.1	5.47%	98.36–103.98

Notes: *P<0.05, **P<0.01 for the generic formulation of levocetirizine under fed condition versus that under fasting condition. ^#p<0.05, ^##p<0.01 for the branded formulation of levocetirizine under fed condition versus that under fasting condition.

Abbreviation: 90% CIs, 90% confidence intervals.

Table 4 P Values Of Multivariate Analysis Of The Generic And The Branded Formulations In Fasting And Fed Conditions

Factors	Fasting Condition (n=22)			Fed Condition (n=23)
	LnCmax	LnAUC0-t	LnAUC0-∞	LnCmax	LnAUC0-t	LnAUC0-∞
Sequence	0.533	0.927	0.870	0.634	0.653	0.654
Cycle	0.659	0.246	0.327	0.634	0.010**	0.010**
Formulation factors	0.826	0.836	0.888	0.101	0.402	0.494
Individual	0.023*	0.000**	0.000**	0.035*	0.000**	0.000**

Notes: *P<0.05, **P<0.01 for the generic formulation versus the branded formulation.

Abbreviations: C_max, the maximal plasma concentration; AUC_0-t, the area under the plasma concentration–time curve; AUC_0-∞, the area under the plasma concentration–time curve extrapolated to infinity.

Figure 2 Mean(±SD) plasma concentration-time profiles of levocetirizine after a single dose of the generic and branded formulations containing 5 mg of levocetirizine for volunteers in (A) Fasting (n=22) and (B) Fed (n=24) states.

Figure 3 Mean(±SD) plasma concentration-time profiles of levocetirizine in fasting (n=22) and fed (n=24) states.