Disposition of Intravenous Paracetamol in Young Women

Pain Clinical Trial

Official title:

Disposition of Intravenous Paracetamol in Young Women, Including During Pregnancy, in Postpartum or When on Oral Contraceptives

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02590900
• Other study ID #: ML6563
• Status: Completed
• Phase: N/A
• First received: October 19, 2015
• Last updated: October 27, 2015
• Start date: June 2010
• Est. completion date: April 2015

Study information

• Verified date: October 2015
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 2015
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• intravenous paracetamol (acetaminophen)
paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

References & Publications (3)

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 — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	paracetamol disposition in young women: total clearance and metabolite specific clearance estimates	pooled analysis of plasma and urine paracetamol and paracetamol metabolite data published in literature in young women following iv paracetamol administration. Samples (plasma and urine) will be collected in the 24 h time interval after initiation of intravenous paracetamol administration (time interval of the PK study)	24 h is the maximal time frame of this pharmacokinetic study (PK is the outcome measured	No