DDMODEL00000267: Paracetamol PK in pregnant and non-pregnant women

  public model
Short description:
This model quantifies the pharmacokinetics of paracetamol and its glucuronide and sulphate metabolites in young women. The impact of pregnancy, time post partum and use of oral contraceptives was investigated.
Original code
  • Paracetamol pharmacokinetics and metabolism in young women.
  • Allegaert K, Peeters MY, Beleyn B, Smits A, Kulo A, van Calsteren K, Deprest J, de Hoon J, Knibbe CA
  • BMC anesthesiology, 11/2015, Volume 15, pages: 163
  • Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium. karel.allegaert@uzleuven.be.
  • 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.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].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.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.
Elke Krekels
Context of model development: Variability sources in PK and PD (CYP, Renal, Biomarkers);
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: This model quantifies the pharmacokinetics of paracetamol and its glucuronide and sulphate metabolites in young women. The impact of pregnancy, time post partum and use of oral contraceptives was investigated. ;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Metabolism;
Annotations are correct.
This model is not certified.
  • Model owner: Elke Krekels
  • Submitted: Dec 13, 2017 4:11:36 PM
  • Last Modified: Dec 14, 2017 1:25:45 PM
Revisions
  • Version: 10 public model Download this version
    • Submitted on: Dec 14, 2017 1:25:45 PM
    • Submitted by: Elke Krekels
    • With comment: Edited model metadata online.
  • Version: 8 public model Download this version
    • Submitted on: Dec 13, 2017 4:11:36 PM
    • Submitted by: Elke Krekels
    • With comment: Edited model metadata online.
 
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