PARAENFO: Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06135389

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Overweight Obesity	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 Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	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)

Arm

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)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Aspartate aminotransferase (ASAT) (UI/L) [24 hours]
Liver function tests
Alanine aminotransferase (ALAT) (UI/L) [24 hours]
Liver function tests
Alkaline Phosphatase PALK (UI/L) [24 hours]
Liver function tests
Bilirubin (μmol/L) [24hours]
Liver function tests
Gamma-Glutamyl transpeptidase (UI/L) [24 hours]
Liver function tests

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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