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A comparison of folic acid pharmacokinetics in obese and nonobese women of childbearing age.

机译:肥胖和非肥胖育龄妇女的叶酸药代动力学比较。

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BACKGROUND: Although maternal folate deficiency during the periconceptional period represents a major risk factor for neural tube defects, obesity has been recognized as an additional risk factor. Studies have identified an increased risk for neural tube defect-affected births among obese mothers even after adjusting for folic acid supplementation. However, although folic acid intake may have been at the recommended dose in these samples, blood folate concentrations were not monitored to ensure that protective levels were reached. Hence, there is a need to compare folic acid pharmacokinetics in obese and nonobese women of childbearing age. METHODS: Healthy obese (n=12) and nonobese (n=12) women of childbearing age volunteered to participate. Each obese participant was matched to a nonobese participant and assigned an equivalent dose of folic acid per kilogram body weight. Folic acid was orally administered after a 6-hour fast, and blood samples were taken over a 10-hour period to evaluate pharmacokinetic parameters. RESULTS: Area under the time-concentration curve (AUC) was found to be significantly higher in the obese group (P=0.008). Defining AUC as a function of dose per kilogram lean body weight (LBW) was found to be a stronger predictor than dose per kilogram total body weight (r=0.90 and 0.76, respectively). CONCLUSIONS: This indicates that the body tightly controls systemic exposure to folic acid, with 90% of the variability in AUC controlled by the dose per kilogram LBW. Periconceptional supplementation recommendations may need to be adjusted to account for LBW differences in the obese population.
机译:背景:尽管在围孕期孕妇叶酸缺乏是神经管缺陷的主要危险因素,但肥胖已被认为是另一种危险因素。研究发现,即使在调整叶酸补充量之后,肥胖母亲中受神经管缺陷影响的出生的风险也会增加。然而,尽管在这些样品中叶酸的摄入量可能已达到推荐剂量,但并未监测血中叶酸的浓度以确保达到保护水平。因此,有必要比较肥胖和非肥胖育龄妇女的叶酸药代动力学。方法:健康肥胖(n = 12)和非肥胖(n = 12)育龄妇女自愿参加。将每个肥胖参与者与非肥胖参与者匹配,并为其每千克体重分配等效剂量的叶酸。禁食6小时后口服叶酸,并在10小时内采集血样以评估药代动力学参数。结果:肥胖组的时间-浓度曲线下面积(AUC)明显更高(P = 0.008)。发现将AUC定义为每千克瘦体重(LBW)的剂量的函数比每千克总体重的剂量具有更强的预测性(分别为r = 0.90和0.76)。结论:这表明机体严格控制全身性暴露于叶酸中,其中90%的AUC变异性受每千克LBW剂量控制。可能需要调整围产期补充建议,以解决肥胖人群中LBW的差异。

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