Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

Conditions
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Overweight, Obesity

Intervention / Treatment
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* Biological: Titration of paracetamol and its metabolites - scheme1
* Biological: Titration of paracetamol and its metabolites - scheme 2


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| blood sampling scheme1<br>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<br>* 15 to 20 minutes and 1 to 2 hours after first perfusion and before second perfusion/administration of paracetamol<br>|
| blood sampling scheme2<br>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<br>* 30 to 40' after first perfusion and before second perfusion/administration of paracetamol (residual concentration)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Overweight, population pharmacokinetics, paediatrics