Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers
Background: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogr...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00643/full |
| _version_ | 1818136724760428544 |
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| author | Xiaojiao Li Cai Liu Xiaoxue Zhu Haijing Wei Hong Zhang Hong Chen Guiling Chen Deming Yang Hongbin Sun Zhenwei Shen Yifan Zhang Wei Li Jin Yang Yongqiang Liu Xiaojuan Lai Yanchun Gong Xuefang Liu Yongguo Li Dafang Zhong Junqi Niu Bin Liu Yanhua Ding |
| author_facet | Xiaojiao Li Cai Liu Xiaoxue Zhu Haijing Wei Hong Zhang Hong Chen Guiling Chen Deming Yang Hongbin Sun Zhenwei Shen Yifan Zhang Wei Li Jin Yang Yongqiang Liu Xiaojuan Lai Yanchun Gong Xuefang Liu Yongguo Li Dafang Zhong Junqi Niu Bin Liu Yanhua Ding |
| author_sort | Xiaojiao Li |
| collection | DOAJ |
| description | Background: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers.Methods: This study was conducted in two parts. Study I was a dose-escalating (5–15 mg) study. For each dose, 15 participants were randomized into three groups (total n = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay.Results: Vicagrel (5–15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (~10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day).Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. The study was registered at http://www.chictr.org.cn (ChiCTR-IIR-16009260). |
| first_indexed | 2024-12-11T09:44:58Z |
| format | Article |
| id | doaj.art-e681599f5b63406da86ab78346c394a6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T09:44:58Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e681599f5b63406da86ab78346c394a62022-12-22T01:12:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.00643383124Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese VolunteersXiaojiao Li0Cai Liu1Xiaoxue Zhu2Haijing Wei3Hong Zhang4Hong Chen5Guiling Chen6Deming Yang7Hongbin Sun8Zhenwei Shen9Yifan Zhang10Wei Li11Jin Yang12Yongqiang Liu13Xiaojuan Lai14Yanchun Gong15Xuefang Liu16Yongguo Li17Dafang Zhong18Junqi Niu19Bin Liu20Yanhua Ding21Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaState Key Laboratory of Natural Medicines and Center of Drug Discovery, College of Pharmacy, China Pharmaceutical University, Nanjing, ChinaFirst Hospital and Institute of Immunology, First Hospital, Jilin University, Jilin, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaCenter of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, ChinaJiangsu Vcare PharmaTech Co. Ltd., Nanjing, ChinaJiangsu Vcare PharmaTech Co. Ltd., Nanjing, ChinaJiangsu Vcare PharmaTech Co. Ltd., Nanjing, ChinaJiangsu Vcare PharmaTech Co. Ltd., Nanjing, ChinaHua Medicine Ltd., Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Hepatology, First Hospital, Jilin University, Jilin, ChinaDepartment of Hand Surgery, First Hospital, Jilin University, Jilin, ChinaPhase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, ChinaBackground: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers.Methods: This study was conducted in two parts. Study I was a dose-escalating (5–15 mg) study. For each dose, 15 participants were randomized into three groups (total n = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay.Results: Vicagrel (5–15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (~10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day).Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. The study was registered at http://www.chictr.org.cn (ChiCTR-IIR-16009260).https://www.frontiersin.org/article/10.3389/fphar.2018.00643/fullvicagrelpharmacokineticspharmacodynamicssafetyclopidogrel |
| spellingShingle | Xiaojiao Li Cai Liu Xiaoxue Zhu Haijing Wei Hong Zhang Hong Chen Guiling Chen Deming Yang Hongbin Sun Zhenwei Shen Yifan Zhang Wei Li Jin Yang Yongqiang Liu Xiaojuan Lai Yanchun Gong Xuefang Liu Yongguo Li Dafang Zhong Junqi Niu Bin Liu Yanhua Ding Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers Frontiers in Pharmacology vicagrel pharmacokinetics pharmacodynamics safety clopidogrel |
| title | Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers |
| title_full | Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers |
| title_fullStr | Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers |
| title_full_unstemmed | Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers |
| title_short | Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers |
| title_sort | evaluation of tolerability pharmacokinetics and pharmacodynamics of vicagrel a novel p2y12 antagonist in healthy chinese volunteers |
| topic | vicagrel pharmacokinetics pharmacodynamics safety clopidogrel |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00643/full |
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