Population Pharmacokinetics of Paracetamol in Overweight and Obese Children (PARAENFO)

The main objective of the study is to define population pharmacokinetic parameters and variability factors for paracetamol and its metabolites in overweight and obese children compared to children with normal weight for age and sex.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Overweight
• Intervention / Treatment: Biological: Titration of paracetamol and its metabolites - scheme1; Biological: Titration of paracetamol and its metabolites - scheme 2

Detailed Description

This study will determine the pharmacokinetic parameters of paracetamol and its metabolites in overweight and obese children compared to children with normal weight for age and sex. The results will enable establishing dosage recommendations for paracetamol in overweight and/or obese children and adolescents.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Florentia KAGUELIDOU, MD, PhD; Phone Number: +33 01 40 03 41 42; Email: florentia.Kaguelidou@aphp.fr
• Study Contact Backup: Name: Karima MESBAHI-IHADJADENE, Project manager; Phone Number: +33 01 58 41 12 11; Email: karima.mesbahi@aphp.fr

Study Locations

• France
  • Paris, France, 75019
    • Robert Debre University Hospital
    • Contact: Florentia KAGUELIDOU, MD, PhD; Phone Number: +33 1 40 03 41 42; Email: florentia.kaguelidou@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Non-obese, overweight and obese children aged 6 to 17 scheduled for surgery requiring intravenous (IV) paracetamol injection intraoperatively.

Description

Inclusion Criteria:

• Child aged 6 to 17 inclusive with normal weight for age and gender (body mass index [BMI]<25kg/m2 adult equivalent at 18 years [IOTF 25]), overweight (body mass index [BMI]≥ 25kg/m2 adult equivalent at age 18 [IOTF 25] and obese (BMI ≥ 30kg/m2 adult equivalent at age 18 [IOTF 30]) for age and sex
• Surgical procedure requiring treatment with paracetamol intravenously as an analgesic
• No opposition by the holder(s) of parental authority

Exclusion Criteria:

• History of chronic anaemia (≤ 5g/100ml)
• History of hepatocellular insufficiency (ASAT, ALAT ≥ 3N)
• History of renal impairment (<60mL/min*1.73m2)
• History of Gilbert's disease
• History of Type 2 diabetes
• Major motor or neurological disability
• Intake of paracetamol within 24 hours before study inclusion (injection of paracetamol IV or oral intake)
• Patients treated with medicinal products known to affect CYP2E1 or UGT (UDP glucuronosyltransferase): isoniazid, antiepileptic drugs (carbamazepine, phenytoin or phenobarbital), antiretroviral and tyrosine kinase inhibitors

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
blood sampling scheme1; 3 strata of 10 children and adolescents - normal weight, overweight and obese Titration of paracetamol (acetaminophen) - scheme 1	Biological: Titration of paracetamol and its metabolites - scheme1; 15 to 20 minutes and 1 to 2 hours after first perfusion and before second perfusion/administration of paracetamol
blood sampling scheme2; 3 strata of 10 children and adolescents - normal weight, overweight and obese Titration of paracetamol (acetaminophen) - scheme 2	Biological: Titration of paracetamol and its metabolites - scheme 2; 30 to 40' after first perfusion and before second perfusion/administration of paracetamol (residual concentration)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of paracetamol and its metabolites: glucuronide, sulfoconjugate, cysteine- and mercapturate-conjugates after a single intravenous perfusion of paracetamol	The overall concentrations (parent drug and metabolites) have the same unit	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspartate aminotransferase (ASAT) (UI/L)	Liver function tests	24 hours
Alanine aminotransferase (ALAT) (UI/L)	Liver function tests	24 hours
Alkaline Phosphatase PALK (UI/L)	Liver function tests	24 hours
Bilirubin (μmol/L)	Liver function tests	24hours
Gamma-Glutamyl transpeptidase (UI/L)	Liver function tests	24 hours

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Sihem BENABOUD, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Overweight; population pharmacokinetics; paediatrics
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Acetaminophen
• Other Study ID Numbers: APHP 201129; 2022-A01743-40 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No