Single -dose and multi -dose bioavailability of isosorbide -5 -mononitrate sustbilityained release capsules in Chinese healthy subjects
10.13699/j.cnki.1001-6821.2015.17.009
- VernacularTitle:单剂量与多剂量口服单硝酸异山梨酯缓释胶囊的人体生物等效性研究
- Author:
Ze-Li CHUN
1
;
Wen-Fang LIU
;
Yang LIN
;
Ke-Xu YANG
;
Gui-Ping ZHAO
;
Chun-Yan LU
;
Li TAN
;
Ying-Chao ZHANG
;
Wei WU
;
Wei SUO
;
Jing LI
;
Zi-Jie ZHOU
;
Hai-Yan DU
;
Qi QIU
;
Ying ZHAO
;
You-Ping LIU
Author Information
1. 沈阳药科大学 药学院
- Keywords:
isosorbide-5-mononitrate;
bioequivalence;
pharmacokinetics;
LC-MS/MS
- From:
The Chinese Journal of Clinical Pharmacology
2015;(17):1727-1731
- CountryChina
- Language:Chinese
-
Abstract:
Objective To compare the pharmacokinetic profiles between a new generic and a branded reference formulation of isosorbide -5 -mononitrate sustained release capsules , and to assess the bioequivalence of the two products in healthy Chinese male subjects.Methods Fifty subjects participated in the open -label, randomized -sequence, 2-way crossover study.Twenty-four subjects and 26 subjects were ran-domly assigned in a 1:1 ratio to receive single dose (50 mg) or multiple dose (50 mg, qd, 6 days) of the test or reference formulation , followed by a one -week washout period and administration of the alternate formulation , respectively.Serial blood samples were collected , and isosorbide -5 -mononitrate concentration in plasma was determined by LC-MS/MS.The relative bioavailability and related parameters of pharmacokinetics were calculated. Results The pharmacokinetic parameters of test formulation and the reference formulation after a single dose were as follows: Cmax were ( 554.18 ± 117.84 ) and (526.29 ±91.58 )μg· L-1; AUC0-t were ( 7834.21 ±1227.70 ) and (7658.86 ±927.74) h· μg· L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 99.82%-113.03%and 99.13%-106.43%of reference formulation , respectively.The pharmacokinetic parame-ters of test formulation and the reference formulation after multiple doses were as follows :Cmax were (612.96 ±171.32) and (527.12 ±114.36 ) μg · L-1; AUC0-t were ( 8408.71 ±1321.91 ) and ( 7781.88 ±1325.12 ) h · μg · L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 108.44% -122.17% and 105.35%-111.57% of reference formulation , respectively.The 90% confidence interval of Cmax and AUC0-t of isosorbide-5-mononitrate for the test formulation after single and multiple oral doses were fall within 70%-143%and 80%-125%of reference formulation.Conclusion The test formulation was considered bioequivalent to the reference formulation.
