ObjectiveWe sought to describe the pharmacokinetics and pharmacodynamics of aspirin through pregnancy (first and third trimester), to identify covariates that significantly impact aspirin pharmacokinetics (PK) and to identify the relationship between aspirin pharmacokinetics and pharmacodynamics (PD). Study DesignThis is a prospective study of patients at high risk for preeclampsia recommended to take 81mg aspirin daily. This study involved three visits: baseline: 1st trimester (10-16’ weeks) 6-hour PK visit, done prior to initiation of aspirin; follow up-1: 2-4 weeks after aspirin initiation; Follow up-2: 3rd trimester 6-hour PK visit (28-32 weeks’). The following were assessed at each visit: weight/BMI, PFA-100 (Siemens), urinary thromboxane B2 (TX-B2), serum thromboxane B2 (TX-B2) and plasma salicylic acid. The PK visits consisted of blood work done at baseline (pre-dose), administration of 81mg non-enteric coated aspirin, and then plasma blood level of salicylic acid assessed at 30minutes and then hourly 1-6 hours after dose. Pearson correlation and multivariable regression were used to identify associations between parameters and identify relevant covariates. Log-adjusted values used for regression analysis. P<0.05 considered significant. ResultsNineteen participants were included with first trimester data, and 16 with third trimester data. There was no statistically significant change in mean PK parameters between the first and third trimester, although there was a trend to lower Cmax in the 3rd vs 1st trimester (p=0.08). In multivariable regression, baseline obesity and current BMI as a continuous measure were negatively associated with log-adjusted peak salicylic acid concentration (-0.28 (-0.46 - -0.11), p=0.003 and -0.02 (-0.03 - -0.009), p=0.001 respectively) and log-adjusted plasma salicylic acid area under the curve 0-6hr post-dose (AUC0-6) (-0.25 (-0.45 – 0.05), p=0.02, -0.04 (-0.07 - -0.01), p=0.008 respectively). There was a significant decrease in urinary thromboxane 2-4 weeks after aspirin initiation compared to baseline, which correlated with a concomitant increase in PFA-100 closure time. In multivariable regression model, there was a strong association between plasma salicylic acid concentration (area under the curve 0-6hrs post-dose) and urinary thromboxane (B=-3.12 (-5.38 - -1.04), p=0.006), and with urinary thromboxane suppression and platelet inhibition, PFA-100 (-0.23 (-0.31 - -0.14), p<0.001). With progressive thromboxane suppression, platelet inhibition (PFA-100 closure time) increased. Individual comorbidities including weight, hypertension, and diabetes, also impacted aspirin response. ConclusionWe have demonstrated the relationship between individual factors, plasma concentrations of salicylic acid, thromboxane suppression, and platelet inhibition at a single dose (81mg) of aspirin taken through pregnancy. Our findings suggest dose modification of aspirin in pregnancy may help to achieve the optimal response. Our results may be used to facilitate computational modeling to identify optimal dosing taking into consideration individual factors