title: Estradiol and weight are covariates of paracetamol clearance in young women.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Estradiol and weight in part explain the variation in paracetamol clearance in young women.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Beleyn
authors.forename: S
authors.initials: S
authors.lastname: Vermeersch
authors.forename: A
authors.initials: A
authors.lastname: Kulo
authors.forename: A
authors.initials: A
authors.lastname: Smits
authors.forename: R
authors.initials: R
authors.lastname: Verbesselt
authors.forename: J N
authors.initials: JN
authors.lastname: de Hoon
authors.forename: K
authors.initials: K
authors.lastname: Van Calsteren
authors.forename: K
authors.initials: K
authors.lastname: Allegaert
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002585:Cesarean Section; D002851:Chromatography, High Pressure Liquid; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016014:Linear Models; D008657:Metabolic Clearance Rate / Q000187:drug effects; D049590:Postpartum Period; D011247:Pregnancy; D012372:ROC Curve
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D003278:Contraceptives, Oral, Hormonal; D000082:Acetaminophen; D004958:Estradiol