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Lookup NU author(s): Raya Vinogradov, Dr Oisín KavanaghORCiD, Dr Jeremy Palmer, Dr Emma Curtis, Professor Farhad Kamali, Professor Steve RobsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)Background: Pregnancy is associated with physiological changes that can alter the pharmacokinetic and pharmacodynamic profile of many drugs. Low-dose aspirin is used for preeclampsia prevention; however, aspirin's pharmacokinetics and pharmacodynamics are poorly studied in pregnant women. Objective: The aim of this study was to compare the pharmacodynamics of 2 common doses of aspirin (75 and 150 mg) used for preeclampsia prevention in high-risk women by examining their effect on thromboxane B2 inhibition. A secondary objective sought to assess if salicylic acid could be used as means to evaluate adherence to aspirin. Study Design: Fourteen pregnant women from a large maternity unit in England, eligible for prophylactic aspirin according to National Institute for Health and Care Excellence guidance, were recruited into 2×2 randomized crossover trial. Blood samples were collected at baseline, 1, 2, 3, 4, 15, 16, 17, 18, and 19 hours postingestion of either 75 or 150 mg of aspirin with a 7-day washout period. Plasma concentrations of salicylic acid, the primary metabolite of aspirin, were determined using high performance liquid chromatography. Pharmacodynamic response to aspirin was assessed by measuring serum thromboxane B2 concentrations by an enzyme-linked immunosorbent assay. Analyte data were compared using nonparametric test statistics for paired values (Wilcoxon Signed Rank Test) and areas under serum SA concentration versus time curve. Pharmacokinetic modeling was used to bridge the data arising from the overnight sampling break. Results: A single dose of 150 mg of aspirin produced higher plasma exposure of SA in comparison to 75 mg (median SA areas under serum SA concentration vs time curve0–19 16.7 μg∗h/ml [interquartile range 15.2–19.3] vs 6.8 μg∗h/ml [interquartile range 6.1–8.3], P<.001). Pharmacokinetic models suggest that plasma SA concentrations could be detected above the maximum concentration recorded at baseline for the first 11 hours after 75 mg and for 12 hours after 150-mg aspirin dosing, providing a time frame to confirm recent aspirin ingestion. The 150-mg aspirin dose produced a greater normalized reduction in serum thromboxane B2 (median normalized reduction 95.7% [interquartile range 92.6%–97.3%] than the 75-mg dose median normalized reduction 84.6% [interquartile range 77.3%–92.3%], P<.007). Conclusion: Compared to the 75-mg dose, 150 mg of aspirin more effectively inhibits thromboxane B2, providing rationale for further investigation of effectiveness of higher doses for preeclampsia prevention. Despite limitations, measuring serum SA concentration could still be used in future models to test adherence if done within 11 to 12 hours after ingestion.
Author(s): Vinogradov R, Kavanagh ON, Palmer J, Murphy P, Curtis E, Kamali F, Robson S
Publication type: Article
Publication status: Published
Journal: American Journal of Obstetrics and Gynecology
Year: 2024
Pages: epub ahead of print
Online publication date: 21/10/2024
Acceptance date: 14/10/2024
Date deposited: 02/12/2024
ISSN (print): 0002-9378
ISSN (electronic): 1097-6868
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ajog.2024.10.023
DOI: 10.1016/j.ajog.2024.10.023
Data Access Statement: Data availability: Data are available upon request from the corresponding author. To gain access, data requestors will need to sign a data access agreement. Data available: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices), and study protocol. Investigators, who proposed the use of the data, have been approved by an independent review committee.
PubMed id: 39442643
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