Investigation of potential pharmacokinetic interaction between the Fixed-Dose-Combination of perindopril/indapamide/amlodipine compared with Fixed-Dose-Combination of perindopril/indapamide and amlodipine the in healthy Chinese volunteers

Preprint | 
10.55415/deep-2023-0009.v1
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Huitao Gao#
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Hongzhong Liu#
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xin Zheng
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xinge Cui
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Stephanie Bricout-Hennel
Institut de Recherches Internationales Servier, France
Institut de Recherches Internationales Servier, France
Arnaud Lucien
Institut de Recherches Internationales Servier, France
Institut de Recherches Internationales Servier, France
Pauline Lauruol
Institut de Recherches Internationales Servier, France
Institut de Recherches Internationales Servier, France
Yaqin Wang
SERVIER (Beijing) Pharmaceutical Research & Development Co., Ltd, China
SERVIER (Beijing) Pharmaceutical Research & Development Co., Ltd, China
Xue Wang
SERVIER (Beijing) Pharmaceutical Research & Development Co., Ltd, China
SERVIER (Beijing) Pharmaceutical Research & Development Co., Ltd, China
Hongyun Wang*
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chen Rui*
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

# contributed equally to this work, * Corresponding author


Abstract

S05590 is a fixed-dose combination of perindopril tert-butylamine 4 mg/indapamide 1.25 mg, and S06593 is a fixed-dose combination of perindopril arginine 5 mg/indapamide 1.25 mg/amlodipine 5 mg. The purpose of this study was to determine whether there were pharmacokinetic interactions between the components of S06593, which uses S05590 and amlodipine as reference drugs in Chinese healthy male volunteers after a single oral administration under fasting conditions. Thus, a single-center, open-label, randomized, three-period, six-way crossover study was conducted. A total of 42 subjects were enrolled and randomized to receive S05590 plus amlodipine, or S06593. The doses of perindopril were 3.34 mg in both S05590 and S06593 calculated as free acid. Blood samples were collected in each treatment period to determine the plasma concentrations of perindopril, indapamide, amlodipine, as well as perindoprilat, which is the main metabolite of perindopril. 39 subjects completed this study. The 90% confidence intervals of geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for perindopril, perindoprilat, indapamide and amlodipine were all within the limits (80.00-125.00 %), indicating that S05590 plus amlodipine and S06593 were pharmacokinetic equivalent. During the study, only one serious emergent adverse event (SEAE) was reported, which was considered as not related to study drug by the investigator. And there were no serious treatment-related adverse events in this study.

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