新型磷脂-阿司匹林复合物液体制剂与小剂量肠溶阿司匹林的药代动力学和药效学特征：一项前瞻性、随机、交叉研究的结果。
Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study.
机构信息
Division of Cardiology, University of Florida College of Medicine - Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA.
Department of Medicine, Cardiovascular Research Institute, The University of Vermont, Burlington, VT, USA.
出版信息
J Thromb Thrombolysis. 2022 Oct;54(3):373-381. doi: 10.1007/s11239-022-02687-5. Epub 2022 Aug 29.
Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which can result in subtherapeutic antiplatelet effects. Phospholipid-aspirin liquid filled capsules (PL-ASA) are a novel FDA-approved immediate-release formulation designed to reduce gastrointestinal (GI) injury by limiting direct contact with the stomach lining. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PL-ASA versus EC-ASA at a low dose. This randomized, open-label, crossover study assessed PK and PD following a single 81-mg dose of PL-ASA versus EC-ASA under fasting conditions in 36 volunteers without cardiovascular disease between 18 and 75 years of age. Volunteers were randomly assigned 1:1 to either PL-ASA then EC-ASA or vice versa with a minimum 14-day washout. Assessments included PK parameters for acetylsalicylic acid and salicylic acid, platelet aggregation in response to arachidonic acid (AA), and serum thromboxane B2 (TxB) assessments over 24 h. PL-ASA was rapidly absorbed. PL-ASA reached T 3 h earlier (1.01 vs. 4.00 h, p < 0.0001), with almost double the C (720 vs. 368 ng/mL, p < 0.0001) and overall 44% higher exposure of acetylsalicylic acid (AUC: 601 vs. 416 h*ng/mL, p = 0.0013) compared with EC-ASA. Within 1 h of dosing, PL-ASA achieved significantly lower residual platelet aggregation, which persisted for the full 24 h (median AA-LTA was 47% with PL-ASA vs. 80.5% with EC-ASA; p = 0.0022 at hour-24). Treatment with PL-ASA also resulted in significantly lower serum TxB concentrations at each time point compared with EC-ASA (all p-values < 0.05). PL-ASA resulted in faster and more complete aspirin absorption paralleled by more prompt and potent platelet inhibition compared with EC-ASA after a single 81 mg dose. PL-ASA represents an attractive novel aspirin formulation for the secondary prevention of cardiovascular events.Clinical Trial Registration ClinicalTrials.gov identifier: NCT04811625.
低剂量肠溶阿司匹林（EC-ASA）通常用于二级心血管事件预防。然而，EC 片剂的吸收效果不佳，可能导致抗血小板作用低于治疗剂量。磷脂酰基阿司匹林口服液（PL-ASA）是一种新型的美国 FDA 批准的即刻释放制剂，旨在通过限制与胃内层的直接接触来减少胃肠道（GI）损伤。我们比较了低剂量 PL-ASA 与 EC-ASA 的药代动力学（PK）和药效学（PD）特征。这项随机、开放标签、交叉研究评估了 36 名年龄在 18 至 75 岁之间、无心血管疾病的志愿者在禁食条件下单次给予 81mg PL-ASA 与 EC-ASA 后的 PK 和 PD。志愿者按 1:1 随机分配至 PL-ASA 组或 EC-ASA 组，洗脱期至少 14 天。评估包括乙酰水杨酸和水杨酸的 PK 参数、花生四烯酸（AA）诱导的血小板聚集以及 24 小时内血清血栓素 B2（TxB）评估。PL-ASA 吸收迅速。PL-ASA 的 T 3h 更早（1.01 比 4.00 小时，p<0.0001），C（720 比 368ng/mL，p<0.0001）几乎翻倍，乙酰水杨酸的总暴露量（AUC：601 比 416h*ng/mL，p=0.0013）高 44%，与 EC-ASA 相比。给药后 1 小时内，PL-ASA 达到的残余血小板聚集明显较低，持续了整整 24 小时（中位 AA-LTA 为 47%，PL-ASA 组；80.5%，EC-ASA 组；p=0.0022 时-24 小时）。与 EC-ASA 相比，PL-ASA 治疗还导致每个时间点的血清 TxB 浓度显著降低（所有 p 值均<0.05）。与 EC-ASA 相比，单次 81mg 剂量后，PL-ASA 导致更快、更完全的阿司匹林吸收，同时更迅速、更强效的血小板抑制。PL-ASA 是一种有吸引力的新型阿司匹林制剂，可用于二级心血管事件预防。临床试验注册ClinicalTrials.gov 标识符：NCT04811625。
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