A pharmacokinetic assessment of optimal dosing, preparation, and chronotherapy of aspirin in pregnancy.

BACKGROUND: The benefit of aspirin in preventing preeclampsia is well established; however, studies over the years have demonstrated variability in outcomes with its use. Potential contributing factors to this variation in efficacy include dosing, time of dosing, and preparation of aspirin. OBJECTIVE: We aimed to compare the difference in pharmacokinetics of aspirin, through its major active metabolite, salicylic acid, in pregnant women and nonpregnant women, and to examine the effect of dose (100 mg vs 150 mg), preparation (enteric coated vs non-enteric-coated), and chronotherapy of aspirin (morning vs evening) between the 2 groups. MATERIALS AND METHODS: Twelve high-risk pregnant women and 3 nonpregnant women were enrolled in this study. Pregnant women were in 1 of 4 groups (100 mg enteric coated, 100 mg non-enteric-coated, 150 mg non-enteric-coated morning dosing, and 150 mg non-enteric-coated evening dosing), whereas nonpregnant women undertook each of the 4 dosing schedules with at least a 30-day washout period. Blood samples were collected at baseline (before ingestion) and at 1, 2, 4, 6, 12, and 24 hours after ingestion of aspirin. Plasma obtained was analyzed for salicylic acid levels by means of liquid chromatography-mass spectrometry. Pharmacokinetic values of area under the curve from time point 0 to 24 hours point of maximum concentration, time of maximum concentration, volume of distribution, clearance, and elimination half-life were analyzed for statistical significance with SPSS v25 software. RESULTS: Pregnant women had a 40% ± 4% reduction in area under the curve from time point 0 to 24 hours (P < .01) and 29% ± 3% reduction in point of maximum concentration (P < .01) with a 44% ± 8% increase in clearance (P < .01) in comparison to that in nonpregnant women when 100 mg aspirin was administered. The reduction in the area under the curve from time point 0 to 24 hours, however, was minimized with the use of 150 mg aspirin in pregnant women, with which the area under the curve from time point 0 to 24 hours was closer to that achieved with the use of 100 mg aspirin in nonpregnant women. There was a 4-hour delay (P < .01) in the time of maximum concentration, a 47% ± 3% reduction in point of maximum concentration (P < .01) and a 48% ± 1% increase in volume of distribution (P < .01) with the use of 100 mg enteric-coated aspirin compared to non-enteric-coated aspirin, with no difference in the overall area under the curve. There was no difference in the pharmacokinetics of aspirin between morning and evening dosing. CONCLUSION: There is a reduction in the total drug metabolite concentration of aspirin in pregnancy, and therefore a dose adjustment is potentially required in pregnant women. This is likely due to the altered pharmacokinetics of aspirin in pregnancy, with an increase in clearance. There was no difference in the total drug metabolite concentration of aspirin between enteric-coated and non-enteric-coated aspirin and between morning and evening dosing of aspirin. Further pharmacodynamic and clinical studies are required to examine the clinical relevance of these pharmacokinetic findings.

Associations between family history of cardiovascular disease, knowledge of cardiovascular disease risk factors and health behaviours.

The objective of the study was to examine associations between family history of premature cardiovascular disease (CVD), knowledge of CVD risk and protective factors, and health behaviours. The design was via administration of a questionnaire to 307 participants from four general practice centre waiting rooms in the Sydney West area. The most recognised CVD risk factor was smoking (97.7%) and the most recognised CVD protective factor was omega-3 fatty acids (78.5%). After adjustment for age, sex, education attainment and personal history of CVD, a strong family history of premature CVD was associated with being more likely to interpret a blood pressure of 130/85 as a CVD risk factor (OR 2.77, 95% CI 1.07-7.14), but less likely to identify being an ex-smoker (compared with never having smoked before) as a risk factor (OR 0.32, 95% CI 0.12-0.90). Those with a strong family history of premature CVD, on average, had smoked 0.82 pack years more than those with an average family history of premature CVD (s.e. 4.22, P=0.04). In conclusion, there continues to be both strengths and deficits in the community's overall knowledge of CVD risk and protective factors, and a strong family history of premature CVD appears to be an independent risk factor for smoking.

Vitamin D status and its predictive factors in pregnancy in 2 Australian populations.

BACKGROUND: High prevalence rates of suboptimal vitamin D levels have been observed in women who are not considered 'at risk'. The effect of behavioural factors such as sun exposure, attire, sunscreen use and vitamin D supplementation on vitamin D levels in pregnancy is unknown. AIM: To determine prevalence and predictive factors of suboptimal vitamin D levels in 2 antenatal clinics in Australia--Campbelltown, NSW and Canberra, ACT. METHODS: A cross-sectional study of pregnant women was performed with a survey of demographic and behavioural factors and a mid-pregnancy determination of maternal vitamin D levels. RESULTS: The prevalence of vitamin D deficiency (≤25 nmol/L) and insufficiency (26-50 nmol/L) was 35% in Canberra (n=100) and 25.7% in Campbelltown (n=101). The majority of participants with suboptimal D levels had vitamin D insufficiency. Among the vitamin D-deficient women, 38% were Caucasian. Skin exposure was the main behavioural determinant of vitamin D level in pregnancy in univariate analysis. Using pooled data ethnicity, season, BMI and use of vitamin D supplements were the main predictive factors of suboptimal vitamin D. Vitamin D supplementation at 500 IU/day was inadequate to prevent insufficiency. CONCLUSIONS: Behavioural factors were not as predictive as ethnicity, season and BMI. As most participants had one of the predictive risk factors for suboptimal vitamin D, a case could be made for universal supplementation with a higher dose of vitamin D in pregnancy and continued targeted screening of the women at highest risk of vitamin D deficiency.

Time poor: rushing decreases the accuracy and reliability of blood pressure measurement technique in pregnancy.

BACKGROUND: In pregnancy, absolute blood pressure (BP) limits define preeclampsia. Therefore, BP in pregnancy should be measured accurately and in accordance with accepted guidelines. Accuracy of BP readings determined by rate of cuff deflation was analyzed. This study also investigated the compliance of clinical staff at Royal Prince Alfred Hospital, Australia, to guidelines for BP measurement. METHODS: The study was an observational trial of 98 normotensive antenatal or recently postnatal patients. Two BP readings were taken, each with fast (>5 mm Hg/sec) and slow (