Oral Presentation Society of Obstetric Medicine of Australia and New Zealand ASM 2018

A pharmacokinetic assessment of aspirin through timed analysis of plasma salicylate acid level: an analysis of the difference in gender, dose and preparation of aspirin. (#8)

Renuka Dr Shanmugalingam 1 2 3 , XiaoSuo Dr Wang 4 , Katrina Dr Chau 3 5 , Bei Dr Xu 3 , Gaksoo Ms Lee 2 , Roshika Ms Kumar 2 , Annemarie Prof Hennessy 1 2 3 , Angela Prof Makris 1 2 3
  1. School of Medicine, Western Sydney University, Sydney, NSW, Australia
  2. Renal Medicine, South Western Sydney Local Health District, Liverpool, NSW, Australia
  3. Vascular Immunology, Heart Research Institue, Newtown, NSW, Australia
  4. Bosch Mass Spectrometry Facility, Bosch Institute, Sydney Medical School, University of Sydney, Newtown, NSW, Australia
  5. School of Medicine, University of Sydney, SYDNEY, NSW, Australia

Introduction

The benefit of aspirin in preventing preeclampsia is well established. Recent data, however, suggest variability in outcomes with its use. Two potential contributing factors are the dose and preparation of aspirin.

Objective/Hypothesis:

To determine the:

  • Pharmacokinetics of 100mg coated (Coated100) vs 100mg non-coated (NonCoated100) vs 150mg non-coated (NonCoated150) aspirin
  • Pharmacokinetics of the above in male vs non-pregnant vs gestation-matched pregnant female subjects

Methods

Three subjects from each group were given Coated100, NonCoated100 or NonCoated150 aspirin at different times. Blood samples were collected pre-ingestion, 1-hour post, 2-hours post, 4-hours post, 6-hours post, 12-hours post and 24-hours post-ingestion of aspirin. Samples were analysed for plasma salicylate acid (SA) utilising a validated liquid chromatography-mass spectrometry (LCMS) methodology. The differences in the area under the curves (AUC) were analysed using Kruskal-Wallis and Mann-Whitney-U (SPSS).

Results

The AUCs of Coated100, NonCoated100 and NonCoated150 were different across all three groups of subjects (p<0.001). When compared between dose-matched differing preparations, there was no significant difference in AUCs between Coated100 and NonCoated100 in all groups (p=0.2). When compared for preparation-matched differing doses, AUCs for NonCoated150 and NonCoated100 was significantly different (p=0.001). The was a statistically significant difference in AUCs between the sexes (p = 0.04) and a difference in AUCs between pregnant and non-pregnant females with lower AUCs in pregnant females (p = 0.03). The difference in AUCs between pregnant and non-pregnant females, however, was lost when corrected for 150mg of aspirin(p=0.98).

Conclusion

The pharmacokinetics of aspirin between male, non-pregnant and pregnant female differs, with lower AUCs in pregnant females. There is no difference in the dose-matched AUCs between coated and non-coated aspirin but a difference was noted in AUCs between preparation-matched 100mg and 150mg of Aspirin. The clinical significance of this in the high-risk pregnant women is yet to be examined, however, potentially supports the need for a higher dose of aspirin in pregnant women