AUTHOR=Ye Zekang , Chen Pengsheng , Tan Chuchu , Gong Xiaoxuan , Li Ran , Dong Zhou , Ullah Inam , Zhou Chen , Zhou Sufeng , Xie Lijun , Hou Xuemei , Han Zhihui , Gu Qian , Ma Jiazheng , Teng Jianzhen , Tang Yingdan , Zhang Zhuanxia , Hu Haitang , Zhuang Quankun , Chen Juan , Zhu Bei , Shao Feng , Li Chunjian 

TITLE=Effects of ilaprazole on the steady-state pharmacodynamics of clopidogrel in healthy volunteers: An open-label randomized crossover study

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.952804

DOI=10.3389/fphar.2022.952804

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel.</p><p><bold>Methods:</bold> A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 μmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y<sub>12</sub> assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of &gt;40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing.</p><p><bold>Results:</bold> IPA was comparable between the two regimens at 0, 10 and 24 h (<italic>p</italic> &gt; 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, <italic>p</italic> = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens.</p><p><bold>Conclusion:</bold> In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant.</p><p><bold>Clinical Trial Registration</bold>: [<ext-link ext-link-type="uri" xlink:href="http://www.chictr.org.cn/" xmlns:xlink="http://www.w3.org/1999/xlink">www.chictr.org.cn</ext-link>], identifier [ChiCTR2000031482].</p>