POPULATION PHARMACOKINETICS OF PANTOPRAZOLE IN PATIENTS ON DUAL ANTIPLATELET THERAPY FOLLOWING ACUTE CORONARY SYNDROME

V. Nikolić, D. Stokanović, Slobodan M Janković, Sandra S. Konstatinović, J. Zvezdanović, Jelena Lilić, Nikola Stefanović, S. Apostolovic, J. Milovanović
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Abstract

This study investigates factors influencing pantoprazole pharmacokinetics (PK) in patients with acute coronary syndrome (ACS) undergoing dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid and clopidogrel, alongside concomitant pantoprazole to mitigate gastrointestinal risks. We conducted a prospective analysis on 93 ACS patients, assessing pantoprazole PK parameters and their correlation with C-reactive protein (CRP) levels, indicative of inflammation. Blood samples for pantoprazole concentration and CRP levels were collected according to a predefined schedule, post-oral pantoprazole administration at steady state. The study highlights a notable influence of CRP levels on pantoprazole clearance, underscoring inflammation’s impact on drug metabolism. Elevated CRP was associated with altered pantoprazole pharmacokinetics, suggesting that inflammatory status significantly contributes to metabolic variability in this patient population. Our findings suggest the need for personalized pantoprazole dosing in ACS patients on DAPT, considering the inflammatory status as reflected by CRP levels. This approach could optimize therapeutic efficacy and minimize adverse effects, advancing personalized treatment strategies in the management of ACS.
急性冠状动脉综合征后接受双重抗血小板疗法的患者体内泮托拉唑的群体药代动力学
本研究调查了影响急性冠状动脉综合征(ACS)患者泮托拉唑药代动力学(PK)的因素,这些患者正在接受由乙酰水杨酸和氯吡格雷组成的双联抗血小板疗法(DAPT),并同时接受泮托拉唑治疗以降低胃肠道风险。我们对 93 例 ACS 患者进行了前瞻性分析,评估泮托拉唑的 PK 参数及其与指示炎症的 C 反应蛋白 (CRP) 水平的相关性。根据预先确定的时间表,在稳定状态下口服泮托拉唑后采集血样,以检测泮托拉唑浓度和 CRP 水平。研究强调了 CRP 水平对泛普拉唑清除率的显著影响,突出了炎症对药物代谢的影响。CRP 升高与泮托拉唑药代动力学的改变有关,这表明炎症状态在很大程度上导致了这类患者的代谢变化。我们的研究结果表明,考虑到 CRP 水平所反映的炎症状态,需要对接受 DAPT 的 ACS 患者进行个性化的泮托拉唑给药。这种方法可以优化疗效,减少不良反应,从而推进 ACS 治疗中的个性化治疗策略。
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