The effect of maternal body mass index on optimal dosing of aspirin for preeclampsia prevention

To compare the pharmacokinetic (PK) properties of two doses of aspirin (ASA) in pregnant and non-pregnant people with and without obesity (BMI >30 kg/m2). Sixteen pregnant and 16 non-pregnant aspirin-naïve people were prospectively enrolled in a convenience sampling study. Those already taking ASA, had used ASA within last week, or have ASA allergy were excluded. After enrollment, people were randomly allocated to 81 or 162 mg of ASA, resulting in two cohorts (pregnant and non-pregnant), each with 4 groups: obese + 81mg, non-obese + 81 mg, obese + 162 mg, and non-obese + 162 mg. Blood samples were collected at baseline (pre-dose) and at 0.5, 1, 2, 4, 6, 12, and 24 hours after ingestion of ASA. Plasma obtained were analyzed for SA (active ingredient of ASA) concentrations using liquid chromatography-mass spectrometry. PK values of area under the curve from time point 0 to 24 hours [AUC(0-24)], point and time of maximum concentration (Cmax and Tmax) were estimated using standard non-compartmental modeling and compared between the groups. Overall, Cmax and AUC(0-24) were lower in pregnant compared with non-pregnant people. Moreover, people with obesity who received 81 mg ASA, had 48±9% and 37±4% lower AUC(0-24) and 58±8% and 43±1% lower Cmax in the non-pregnant and pregnant cohorts compared with those without obesity, respectively. (P< 0.05 in all except Cmax in non-pregnant cohort). However, there were no differences in any in PK parameters between obese and non-obese people who received 162 mg (Figure). Last, there was no difference in AUC(0-24) between pregnant non-obese people who received 81 mg and pregnant obese people on 162 mg (21.43± 6.3 vs. 22.50±15.7 mg/L). Obesity results in a reduction in the total drug metabolite concentration of SA when 81mg of ASA is administrated but not when 162 mg was used. SA concentrations in pregnant people with obesity on 162 mg is equivalent to SA concentrations of pregnant non-obese people on 81 mg. Therefore, increasing the dose of ASA to 162 mg/day is potentially more efficacious in obese pregnant people.