Paracetamol pharmacokinetics and metabolism in young women

BMC Anesthesiology

Catherijne A. J. Knibbe³  Jan de Hoon⁶  Jan Deprest¹  Kristel van Calsteren¹  Aida Kulo⁵  Anne Smits⁴  Bjorn Beleyn²  Mariska Y. Peeters⁷  Karel Allegaert⁴ 

[1]Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium

[2]Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

[3]Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

[4]Department of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium

[5]Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia Herzegovina

[6]Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium

[7]Department of Clinical Pharmacy, St Antonius hospital, Nieuwegein, The Netherlands

关键词: Progesterone;    Pregnancy;    Paracetamol;    Oral contraceptives;    Oestradiol;    Glucuronidation;    Acetaminophen;   

Others  :  1232532
DOI  :  10.1186/s12871-015-0144-3

 received in 2015-04-26, accepted in 2015-11-11,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Allegaert et al.

【 图 表 】

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