Beleyn B, Vermeersch S, Kulo A, Smits A, Verbesselt R, de Hoon J N, Van Calsteren K, Allegaert K
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Gynecol Obstet Invest. 2014;77(4):211-6. doi: 10.1159/000358394. Epub 2014 Mar 25.
Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored.
In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m(2)) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence.
Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m(2), at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001).
Estradiol and weight in part explain the variation in paracetamol clearance in young women.
对乙酰氨基酚的清除率在孕妇与非孕妇之间以及使用或未使用特定口服避孕药（OCs）的女性之间存在差异。然而，女性性激素与对乙酰氨基酚清除率之间的关联从未被探究过。
总共汇集了49名分娩时的女性、8名未使用OCs的女性对照受试者、14名服用OCs女性的历史数据以及15名产后使用和未使用OCs的观察对象，以探究对乙酰氨基酚清除率的协变量。所有人均接受了2克对乙酰氨基酚的单次静脉注射剂量，并在给药后长达6小时采集血样。采用高效液相色谱法定量对乙酰氨基酚。测定至时间无穷大的曲线下面积（AUC0-∞），并通过剂量/AUC0-∞计算清除率（升/小时·平方米）。此外，采用电化学发光酶联免疫吸附测定法对雌二醇和孕酮进行定量。
分娩时对乙酰氨基酚的中位清除率显著高于产后或非孕妇（分别为11.9 vs. 6.42和8.4升/小时·平方米，p至少<0.05），同时观察到对乙酰氨基酚清除率与雌二醇之间存在关联（R = 0.494，p < 0.0001）。在非孕妇中，OCs暴露对对乙酰氨基酚清除率没有影响。多元回归显示对乙酰氨基酚清除率与体重（p = 0.0462）和雌二醇（p < 0.0001）之间存在线性关联（校正R = 0.41，p < 0.001）。
雌二醇和体重部分解释了年轻女性对乙酰氨基酚清除率的差异。
