Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

Population Pharmacokinetics of Paracetamol in Overweight and Obese Children

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.

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.

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