ω-3羧酸与乙酰水杨酸合用时对华法林药代动力学/药效学或血小板功能无影响：两项健康志愿者I期研究结果

No Effect of Omega-3 Carboxylic Acids on Pharmacokinetics/Pharmacodynamics of Warfarin or on Platelet Function When Co-administered with Acetylsalicylic Acid: Results of Two Phase I Studies in Healthy Volunteers.

作者信息

Offman Elliot, Davidson Michael, Nilsson Catarina

机构信息

Certara Strategic Consulting, 2000 Peel Street, Suite 570, Montreal, QC, H3A 2W5, Canada.

University of Chicago Pritzker School of Medicine, Chicago, IL, USA.

出版信息

Am J Cardiovasc Drugs. 2017 Jun;17(3):251-260. doi: 10.1007/s40256-017-0217-4.

DOI:10.1007/s40256-017-0217-4

PMID:28197979

Abstract

BACKGROUND

Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels.

OBJECTIVE

Our objective was to assess the effects of OM3-CA on warfarin pharmacokinetics and pharmacodynamics and on acetylsalicylic acid (ASA)-dependent and independent platelet activation when co-administered with ASA in two phase I studies.

METHODS

In ECLIPSE II (NCT01431690), 26 participants received warfarin 25 mg on days 1 and 22 and OM3-CA 4 g once daily from day 8 to day 28. In OM-EPA-007 (NCT01486433), 52 participants received simvastatin 40 mg plus ASA 81 mg once daily for 14 days, with or without OM3-CA 4 g. Lack of a drug-drug interaction was indicated when 90% confidence intervals (CIs) fell entirely within the range 80-125% for least-squares mean (LSM) ratios of area under the concentration-time curve (AUC), maximum observed plasma concentration (C ), international normalized ratio (INR) AUC to 168 h and maximum INR.

RESULTS

In ECLIPSE II, 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for AUC and C of S- and R-warfarin enantiomers. The 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for INR AUC to 168 h after dosing and for maximum INR of warfarin. In OM-EPA-007, no significant effect of OM3-CA was observed on ASA-dependent or ASA-independent platelet activation. No deaths or serious adverse events occurred in either study.

CONCLUSION

OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA. OM3-CA did not affect platelet function when co-administered with ASA.

摘要

背景

ω-3 羧酸（OM3-CA）可降低甘油三酯水平。

目的

我们的目的是在两项 I 期研究中评估 OM3-CA 与阿司匹林（ASA）合用时对华法林药代动力学和药效学以及对 ASA 依赖性和非依赖性血小板活化的影响。

方法

在 ECLIPSE II（NCT01431690）中，26 名参与者在第 1 天和第 22 天接受 25 mg 华法林，从第 8 天至第 28 天每天接受 4 g OM3-CA。在 OM-EPA-007（NCT01486433）中，52 名参与者每天接受 40 mg 辛伐他汀加 81 mg ASA，持续 14 天，同时服用或不服用 4 g OM3-CA。当浓度-时间曲线下面积（AUC）、最大观察血浆浓度（C）、国际标准化比值（INR）AUC 至 168 小时和最大 INR 的最小二乘均值（LSM）比值的 90%置信区间（CI）完全落在 80-125%范围内时，表明不存在药物相互作用。

结果

在 ECLIPSE II 中，S-和 R-华法林对映体的 AUC 和 C 的 OM3-CA 与无 OM3-CA 的 LSM 比值的 90%CI 落在 80-125%范围内。给药后 INR AUC 至 168 小时以及华法林最大 INR 的 OM3-CA 与无 OM3-CA 的 LSM 比值的 90%CI 落在 80-125%范围内。在 OM-EPA-007 中，未观察到 OM3-CA 对 ASA 依赖性或 ASA 非依赖性血小板活化有显著影响。两项研究均未发生死亡或严重不良事件。