title: Paracetamol pharmacokinetics and metabolism in young women.
abstract: BACKGROUND
  There is relevant between individual variability in paracetamol clearance in young women. In this pooled study, we focused on the population pharmacokinetic profile of intravenous paracetamol metabolism and its covariates in young women.
  
  
  METHODS
  Population PK parameters using non-linear mixed effect modelling were estimated in a pooled dataset of plasma and urine PK studies in 69 young women [47 at delivery, 8/47 again 10-15 weeks after delivery (early postpartum), and 7/8 again 1 year after delivery (late postpartum), 22 healthy female volunteers with or without oral contraceptives].
  
  
  RESULTS
  Population PK parameters were estimated based on 815 plasma samples and 101 urine collections. Compared to healthy female volunteers (reference group) not on oral contraceptives, being at delivery was the most significant covariate for clearance to paracetamol glucuronide (Factor = 2.03), while women in early postpartum had decreased paracetamol glucuronidation clearance (Factor = 0.55). Women on contraceptives showed increased paracetamol glucuronidation clearance (Factor = 1.46). The oestradiol level did not further affect this model. Being at delivery did not prove significant for clearance to paracetamol sulphate, but was higher in pregnant women who delivered preterm (<37 weeks, Factor = 1.34) compared to term delivery and non-pregnant women. Finally, clearance of unchanged paracetamol was dependent on urine flow rate.
  
  
  CONCLUSIONS
  Compared to healthy female volunteers not on oral contraceptives, urine paracetamol glucuronidation elimination in young women is affected by pregnancy (higher), early postpartum (lower) or exposure to oral contraceptives (higher), resulting in at least a two fold variability in paracetamol clearance in young women.
authors.affiliation: NICU, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. karel.allegaert@uzleuven.be.|Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. karel.allegaert@uzleuven.be.
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.affiliation: Department of Clinical Pharmacy, St Antonius hospital, Nieuwegein, The Netherlands. r.peeters@antoniusziekenhuis.nl.
authors.forename: Mariska Y
authors.initials: MY
authors.lastname: Peeters
authors.affiliation: Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. bjorn_beleyn@hotmail.com.|Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. bjorn_beleyn@hotmail.com.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Beleyn
authors.affiliation: NICU, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. anne.smits@uzleuven.be.|Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. anne.smits@uzleuven.be.
authors.forename: Anne
authors.initials: A
authors.lastname: Smits
authors.affiliation: Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium. aida.kulo@gmail.com.|Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia Herzegovina. aida.kulo@gmail.com.
authors.forename: Aida
authors.initials: A
authors.lastname: Kulo
authors.affiliation: Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. kristel.vancalsteren@uzleuven.be.|Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium. kristel.vancalsteren@uzleuven.be.
authors.forename: Kristel
authors.initials: K
authors.lastname: van Calsteren
authors.affiliation: Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. jan.deprest@uzleuven.be.|Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium. jan.deprest@uzleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. jan.dehoon@uzleuven.be.|Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium. jan.dehoon@uzleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: de Hoon
authors.affiliation: Department of Clinical Pharmacy, St Antonius hospital, Nieuwegein, The Netherlands. c.knibbe@antoniusziekenhuis.nl.|Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. c.knibbe@antoniusziekenhuis.nl.
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D049590:Postpartum Period; D011247:Pregnancy; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen