Clinical RD, AstraZeneca RD, Mölndal, Sweden.
Am J Cardiovasc Drugs. 2012 Aug 1;12(4):217-24. doi: 10.1007/BF03261830.
The absence of a pharmacokinetic interaction between the proton pump inhibitor esomeprazole (40 mg) and acetylsalicylic acid (aspirin, ASA; 325 mg) has previously been established.
This study set out to investigate the potential for pharmacodynamic interaction between low-dose ASA and esomeprazole in healthy volunteers, by measuring ASA antiplatelet activity.
This was a single-center, open-label, two-period, randomized crossover study.
Healthy male and female volunteers aged 18-75 years were included. All volunteers received ASA 81 mg once daily for 5 days prior to the study (pre-screen). Subjects were eligible for inclusion if they had aspirin reactivity units (ARU, as measured by the VerifyNow ASA assay) of <550 on Day 6.
After pre-screening and a washout period of at least 14 days, eligible volunteers received ASA 81 mg with or without esomeprazole 20 mg once daily for 5 days in randomized order, with a 14-day washout between treatments.
The main outcome measure was the antiplatelet activity of ASA, as assessed by ARU ratio relative to baseline in the VerifyNow ASA assay; suppression of serum thromboxane B(2) (TXB(2)) was a secondary endpoint. Statistical comparisons were made using linear mixed models.
A total of 29 volunteers (19 aged ≥50 years; 8 women; 21 men) were evaluable for pharmacodynamic analysis (per protocol). All volunteers on both treatments achieved ARU <550 at Day 6. The geometric mean ratio of Day 6 to Day 1 (baseline) platelet aggregation was 0.70 (95% confidence interval [CI] 0.68, 0.72) with ASA alone and 0.71 (95% CI 0.69, 0.74) with ASA + esomeprazole. The ratio of platelet aggregation (ASA + esomeprazole/ASA) was 1.02 (95% CI 0.99, 1.05). ASA administered alone or with esomeprazole reduced serum TXB(2) by more than 99.5%. The ratio of suppression of serum TXB(2) levels (ASA + esomeprazole/ASA) was 1.06 (95% CI 0.88, 1.29). The combination of ASA and esomeprazole was well tolerated.
No pharmacodynamic interaction between low-dose ASA and esomeprazole was found with regard to platelet function.
Registered at ClinicalTrials. gov as NCT01199328.
质子泵抑制剂埃索美拉唑（40 毫克）和乙酰水杨酸（ASA；325 毫克）之间不存在药代动力学相互作用，这一点先前已经得到证实。
本研究旨在通过测量 ASA 抗血小板活性，研究低剂量 ASA 和埃索美拉唑之间是否存在药效学相互作用。
这是一项单中心、开放标签、两周期、随机交叉研究。
年龄在 18-75 岁的健康男性和女性志愿者入选。所有志愿者在研究前（预筛查）均接受每日一次 ASA 81 毫克，连续 5 天。如果第 6 天的阿司匹林反应单位（ARU，通过 VerifyNow ASA 测定）<550，则符合入选条件。
预筛查和至少 14 天洗脱期后，符合条件的志愿者以随机顺序接受每日一次 ASA 81 毫克加或不加埃索美拉唑 20 毫克，连续 5 天，两种治疗之间有 14 天洗脱期。
主要观察指标为 ARU 比值相对于 VerifyNow ASA 测定中的基线，评估 ASA 的抗血小板活性；抑制血清血栓素 B2（TXB2）为次要终点。使用线性混合模型进行统计学比较。
共有 29 名志愿者（≥50 岁 19 名；女性 8 名；男性 21 名）符合药效学分析（按方案）的条件。所有志愿者在两种治疗方案下均于第 6 天达到 ARU<550。第 6 天相对于第 1 天（基线）的血小板聚集的几何均数比值分别为单独使用 ASA 时为 0.70（95%置信区间 [CI] 0.68，0.72）和 ASA 加埃索美拉唑时为 0.71（95% CI 0.69，0.74）。血小板聚集比值（ASA+埃索美拉唑/ASA）为 1.02（95% CI 0.99，1.05）。单独使用 ASA 或联合使用埃索美拉唑可使血清 TXB2 降低超过 99.5%。抑制血清 TXB2 水平的比值（ASA+埃索美拉唑/ASA）为 1.06（95% CI 0.88，1.29）。ASA 和埃索美拉唑联合使用耐受良好。
在血小板功能方面，低剂量 ASA 和埃索美拉唑之间未发现药效学相互作用。
ClinicalTrials.gov 注册号为 NCT01199328。
