PMID- 37814929 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20231102 IS - 2160-7648 (Electronic) IS - 2160-763X (Linking) VI - 12 IP - 11 DP - 2023 Nov TI - Pharmacokinetics and Drug-Drug Interaction of Allisartan Isoproxil and Indapamide Sustained-Release Formulation. PG - 1051-1059 LID - 10.1002/cpdd.1321 [doi] AB - Allisartan isoproxil (AI) is an angiotensin II type 1 receptor blocker and be converted into the active substance EXP3174 in vivo. We evaluated the drug-drug interactions of AI and an indapamide sustained-release (Ind SR) preparation, as well as the pharmacokinetic characteristics and safety of AI and Ind SR in healthy subjects. The trial was set up in 6 sequences and 3 cycles, and each cycle contained a 7-day washout period. Subjects received 3 different trial drugs (A, AI; B, Ind SR; C, AI + Ind SR) during 3 different cycles. Twenty-four subjects were enrolled in the clinical trial. Of these, 22 completed the study, 2 subjects dropped out due to adverse events (AEs). For subjects given AI alone or combined with Ind SR, the pharmacogenetic parameters C(max) and the geometric mean ratio of steady state (combined/single) of EXP3174 was 130%. The geometric mean ratio of area under the concentration-time curve over the dosing interval at steady state (combined/single use) was 144.5%. Therefore, the combination of Ind SR had an impact on the pharmacokinetics of AI. Then, the results indicated that the AI combination had no effect on the pharmacokinetics of Ind SR. Serious AEs did not occur. The AEs in this clinical trial were the same as those for AI and Ind SR. Combined administration resulted in 2 cases (2 subjects) of Grade 3 hypotension and 1 case of Grade 3 hypotension with AI alone. Considering that this trial included healthy volunteers, the risk of hypotension was expected to be manageable. CI - (c) 2023, The American College of Clinical Pharmacology. FAU - Yi, Wu AU - Yi W AD - Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China. AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Lin, Sisi AU - Lin S AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Hao, Rui AU - Hao R AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Shao, Yiming AU - Shao Y AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Wang, Yannan AU - Wang Y AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Yu, Jin AU - Yu J AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Fang, Lu AU - Fang L AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Zhu, Jingjing AU - Zhu J AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Wang, Aiwei AU - Wang A AD - Fuyang First People's Hospital, Hangzhou, Zhejiang, China. FAU - Wu, Yanfang AU - Wu Y AD - Fuyang First People's Hospital, Hangzhou, Zhejiang, China. FAU - Huang, Hua AU - Huang H AD - Shenzhen Salubris Pharmaceuticals Co., Ltd, Shenzhen, China. FAU - Deng, Chongyang AU - Deng C AD - Shenzhen Salubris Pharmaceuticals Co., Ltd, Shenzhen, China. FAU - Sun, Jingchao AU - Sun J AD - Shenzhen Salubris Pharmaceuticals Co., Ltd, Shenzhen, China. FAU - Zhao, Hongcan AU - Zhao H AD - Hangzhou First People's Hospital, Hangzhou, Zhejiang, China. FAU - Wang, Ying AU - Wang Y AD - Center for Clinical Pharmacy, Cancer Center, Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Tong, Xiangming AU - Tong X AD - Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China. AD - Cancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231010 PL - United States TA - Clin Pharmacol Drug Dev JT - Clinical pharmacology in drug development JID - 101572899 RN - F089I0511L (Indapamide) RN - GD76OCH73X (losartan carboxylic acid) RN - 0 (allisartan isoproxil) RN - 0 (Delayed-Action Preparations) SB - IM MH - Humans MH - *Indapamide/adverse effects/pharmacokinetics MH - Delayed-Action Preparations MH - Drug Interactions MH - *Hypotension/chemically induced OTO - NOTNLM OT - allisartan isoproxil OT - combined administration OT - hypertension OT - indapamide OT - pharmacokinetic OT - safety EDAT- 2023/10/10 06:41 MHDA- 2023/11/02 12:45 CRDT- 2023/10/10 05:30 PHST- 2022/06/27 00:00 [received] PHST- 2023/07/27 00:00 [accepted] PHST- 2023/11/02 12:45 [medline] PHST- 2023/10/10 06:41 [pubmed] PHST- 2023/10/10 05:30 [entrez] AID - 10.1002/cpdd.1321 [doi] PST - ppublish SO - Clin Pharmacol Drug Dev. 2023 Nov;12(11):1051-1059. doi: 10.1002/cpdd.1321. Epub 2023 Oct 10.