Bioequivalence study of levodopa and benserazide hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions

doi:10.12092/j.issn.1009-2501.2026.07.005

Abstract

Abstract:

AIM: To evaluate the bioequivalence of generic and original levodopa-benserazide tablets in healthy Chinese subjects under fasting and fed conditions. METHODS: A randomized, open-label, single-dose, two-sequence, four-period, fully replicated crossover study design was employed. A total of 64 healthy subjects were enrolled, with 32 subjects in the fasting group and 32 in the fed group, each divided into two groups of 16 subjects. Each subject received either one tablet of the test formulation or one tablet of the reference formulation in each period, with a washout period of 5 days between doses. The plasma concentrations of levodopa and tri-hydroxybenzylhydrazine were measured using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using WinNonlin 8.1 software to assess the bioequivalence of the two formulations. RESULTS: Under fasting conditions, the C_max of levodopa for the test and reference formulations were (4261.10±1709.86) ng/mL and (4157.00±1538.07) ng/mL, respectively. The AUC_0-t values were (7427.57±1409.34) h·ng·mL^?1 and (7060.07±1389.62) h·ng·mL^?1, while AUC_0-∞ values were (7472.97±1411.51) h·ng·mL^?1 and (7146.98±1295.45) h·ng·mL^?1, respectively. For tri-hydroxybenzylhydrazine, C_max values were (27.99±13.38) ng/mL and (26.56±14.06) ng/mL; AUC_0-t were (17.85±6.00) h·ng·mL^?1 and (17.22±5.39) h·ng·mL^?1, respectively; and AUC_0-∞values were (19.00±6.39) h·ng·mL^?1 and (18.39±5.85) h·ng·mL^?1, respectively. In the fed trials, the C_max of levodopa for the test and reference formulations were (3338.28±1493.52) ng/mL and (3325.30±1524.62) ng/mL, respectively; AUC_0-t values were (6744.79±1325.04) h·ng·mL^?1 and (6615.38±1364.12) h·ng·mL^?1, respectively; and AUC_0-∞ values were (6786.27±1326.03) h·ng·mL^?1 and (6658.58±1358.30) h·ng·mL^?1, respectively. The C_max, AUC_0-t, and AUC_0-∞ values for trihydroxybenzylhydrazine were (8.35 ± 6.49) and (8.44 ± 6.44) ng/mL, (6.71 ± 4.14) and (6.81 ± 3.79) h·ng·mL^?1, and (7.14 ± 4.27) and (7.23 ± 3.98) h·ng·mL^?1, respectively.The geometric mean ratios of the primary pharmacokinetic parameters for both formulations under fasting and fed conditions fell within the 90% confidence interval of 80.00%-125.00%. A total of 27 adverse events were reported during the study (17 in the fasting group and 10 in the fed group), with no serious adverse events occurring. CONCLUSION: The test formulation demonstrates bioequivalence to the reference formulation in healthy subjects under both fasting and fed conditions, with a favorable safety profile.

Key words: benserazide, bioequivalence, levodopa, tri-hydroxybenzylhydrazine

CLC Number:

R969

Lin LI, Yuming XIA, Chenlin SHEN, Quan XIA, Shuai SONG. Bioequivalence study of levodopa and benserazide hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 899-907.

Figures/Tables 8

References 17

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Group	Age (year)	Weight (kg)	Height (cm)	BMI (kg/m²)
Fasting	31.44±5.29^a	67.03±6.97^a	171.4±5.52^a	22.81±1.86^a
Fasting	31.00±3.69^b	65.33±8.55^b	168.5±7.07^b	22.93±1.78^b
Fed	30.81±4.82^a	67.66±8.20^a	171.9±7.71^a	22.87±2.22^a
Fed	30.13±4.75^b	69.39±8.52^b	172.1±8.03^b	23.38±1.87^b

Group	Age (year)	Weight (kg)	Height (cm)	BMI (kg/m²)
Fasting	31.44±5.29^a	67.03±6.97^a	171.4±5.52^a	22.81±1.86^a
Fasting	31.00±3.69^b	65.33±8.55^b	168.5±7.07^b	22.93±1.78^b
Fed	30.81±4.82^a	67.66±8.20^a	171.9±7.71^a	22.87±2.22^a
Fed	30.13±4.75^b	69.39±8.52^b	172.1±8.03^b	23.38±1.87^b

Parameter	Fasting		Fed
Parameter	Test (n=32)	Reference (n=32)	Test (n=31)	Reference (n=31)
T_max (h)	0.74 (0.33, 3.99)	0.74 (0.33, 3.99)	1.24 (0.50, 4.99)	1.24 (0.49, 4.99)
C_max (ng/mL)	4261.10± 1709.86	4157.00 ± 1538.07	3338.28± 1493.52	3325.30 ± 1524.62
AUC_0-t (h·ng·mL^?1)	7427.57 ± 1409.34	7060.07 ± 1389.62	6744.79± 1325.04	6615.38 ± 1364.12
AUC_0-∞ (h·ng·mL^?1)	7472.97 ± 1411.51	7146.98 ± 1295.45	6786.27 ± 1326.03	6658.58± 1358.30
λ_z (h^?1)	0.37 ± 0.09	0.42 ± 0.11	0.42 ± 0.11	0.41 ± 0.11
t_1/2 (h)	2.06 ± 1.27	1.76 ± 0.48	1.80 ± 0.64	1.82 ± 0.65

Parameter	Fasting		Fed
Parameter	Test (n=32)	Reference (n=32)	Test (n=31)	Reference (n=31)
T_max (h)	0.74 (0.33, 3.99)	0.74 (0.33, 3.99)	1.24 (0.50, 4.99)	1.24 (0.49, 4.99)
C_max (ng/mL)	4261.10± 1709.86	4157.00 ± 1538.07	3338.28± 1493.52	3325.30 ± 1524.62
AUC_0-t (h·ng·mL^?1)	7427.57 ± 1409.34	7060.07 ± 1389.62	6744.79± 1325.04	6615.38 ± 1364.12
AUC_0-∞ (h·ng·mL^?1)	7472.97 ± 1411.51	7146.98 ± 1295.45	6786.27 ± 1326.03	6658.58± 1358.30
λ_z (h^?1)	0.37 ± 0.09	0.42 ± 0.11	0.42 ± 0.11	0.41 ± 0.11
t_1/2 (h)	2.06 ± 1.27	1.76 ± 0.48	1.80 ± 0.64	1.82 ± 0.65

Parameter	Fasting		Fed
Parameter	Test (n=32)	Reference (n=32)	Test (n=31)	Reference (n=31)
T_max (h)	0.49 (0.16, 1.49)	0.49 (0.16, 1.49)	0.99 (0.33, 3.99)	0.75 (0.33, 2.25)
C_max (ng/mL)	27.99 ± 13.38	26.56 ± 14.06	8.35 ± 6.49	8.44 ± 6.44
AUC_0-t (h·ng·mL^?1)	17.85 ± 6.00	17.22 ± 5.39	6.71 ± 4.14	6.81 ± 3.79
AUC_0-∞ (h·ng·mL^?1)	19.00 ± 6.39	18.39 ± 5.85	7.14 ± 4.27	7.23 ± 3.98
λ_z (h^?1)	0.15 ± 0.07	0.17 ± 0.15	0.45 ± 0.24	0.39 ± 0.17
t_1/2 (h)	5.76 ± 3.56	6.06 ± 4.26	2.03 ± 1.23	2.42 ± 1.81