Clinical trial NCT02590900: Disposition of Intravenous Paracetamol in Young Women
Official title: Disposition of Intravenous Paracetamol in Young Women, Including During Pregnancy, in Postpartum or When on Oral Contraceptives
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pain
Keywords: pharmacokinetics
pregnancy
oral contraceptives
oestradiol
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2015-10-29
Enrollment: 69
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pooled analysis of different cohorts of young women who all underwent PK study on paracetamol disposition after iv paracetamol administration.

Brief summary: Compared to early postpartum (10-15 weeks) observations, paracetamol clearance was significantly higher (21.1 vs 11.7 l.h-1, + 80 %) at delivery. This higher clearance was due to a disproportional increase in glucuronidation (11.6 vs 4.76 l.h-1, + 144 %), a proportional increase in oxidation clearance (4.95 vs 2.77 l.h-1, 78 %) and primary renal clearance (1.15 vs 0.75 l.h-1, 53 %) \[KUlo et al, Int J Obstet Anesth\]. This increase in glucuronidation clearance may in part be driven by oestradiol, and may explain within and between individual differences in paracetamol metabolism (e.g. oral contraceptives, follicular vs luteal phase, postpartum, pregnancy, or duration of pregnancy) in young women.

Based on a pooled analysis, investigators aimed to further explore the impact of these covariates on paracetamol metabolism based on plasma and urine collections in women at delivery, in postpartum (early, or late) and healthy volunteers, either or not on oral contraceptives (OC) following intravenous (iv) paracetamol administration.

Detailed description: This study aims to perform a pooled analysis of:

1. Paracetamol PK data recently published in 47 pregnant women. In these cases, iv paracetamol was administered q6h after delivery (caesarean) for 24 h. 8 were recruited a second time for an additional single dose pK study in postpartum (Kulo et al, Br J Clin Pharmacol 2013).
2. The PK data as initially published by Gregoire et al, but limited to female volunteers, all on oral contraceptives (n=14) (Gregoire et al, Clin Pharm Ther 2007)
3. A dataset in 8 young women not on oral contraceptives, iv paracetamol, single dose.

Eligibility criteria: Inclusion Criteria:

1. informed consent
2. for patients (pregnant women at delivery), there has to be a clinical indication (post caesarean analgesia, NPO) to administer iv paracetamol.

Exclusion Criteria:

1. intolerance to paracetamol
2. withdrawal of informed consent.

Primary outcomes:
measure: paracetamol disposition in young women: total clearance and metabolite specific clearance estimates
timeFrame: 24 h is the maximal time frame of this pharmacokinetic study (PK is the outcome measured
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: karel allegaert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beleyn B, Vermeersch S, Kulo A, Smits A, Verbesselt R, de Hoon JN, Van Calsteren K, Allegaert K. Estradiol and weight are covariates of paracetamol clearance in young women. Gynecol Obstet Invest. 2014;77(4):211-6. doi: 10.1159/000358394. Epub 2014 Mar 25.
citation: Kulo A, Peeters MY, Allegaert K, Smits A, de Hoon J, Verbesselt R, Lewi L, van de Velde M, Knibbe CA. Pharmacokinetics of paracetamol and its metabolites in women at delivery and post-partum. Br J Clin Pharmacol. 2013 Mar;75(3):850-60. doi: 10.1111/j.1365-2125.2012.04402.x.
citation: Gregoire N, Hovsepian L, Gualano V, Evene E, Dufour G, Gendron A. Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clin Pharmacol Ther. 2007 Mar;81(3):401-5. doi: 10.1038/sj.clpt.6100064.