Paracetamol and Cefazolin Pharmacokinetics in Normal Weight and Overweight Children (TISSUE)

Pharmacokinetic evaluations will be conducted to characterize the cefazolin plasma concentration-time profile, cefazolin penetration into subcutaneous adipose tissue, and paracetamol metabolization as assessed through blood sampling. The study population consists of children aged 2 to 15 years with either normal weight or overweight. All participants are admitted for a minor elective surgical procedure and will receive paracetamol and/or cefazolin as part of standard perioperative care.

During the procedure, multiple blood and tissue-fluid samples will be collected to quantify paracetamol and cefazolin concentrations in the bloodstream, as well as cefazolin concentrations in subcutaneous adipose tissue. The study aims to characterize drug concentration-time profiles in blood (paracetamol), plasma (cefazolin), and adipose tissue (cefazolin), and to compare these pharmacokinetic parameters between normal-weight and overweight children.

These data are essential to determine whether standard dosing regimens provide adequate drug exposure across different weight categories. Previous research indicates that achieving specific target concentrations in blood and tissue is necessary for optimal therapeutic effect, yet uncertainty remains regarding appropriate dosing in overweight children.

Study Overview

• Status: Recruiting
• Conditions: Paracetamol; Cefazolin
• Intervention / Treatment: Drug: Cefazolin; Drug: Paracetamol (drug)

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Pieter De Cock, Prof. Apr; Phone Number: +32 9 332 29 69; Email: pieter.decock@uzgent.be
• Study Contact Backup: Name: Annemie Bauters, MD.; Phone Number: + 32 9 332 18 83; Email: Annemie.Bauters@UGent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital, Ghent
    • Contact: Anca Amza; Phone Number: +32 9 332 18 83; Email: anca.amza@uzgent.be
    • Principal Investigator: Pieter De Cock, Prof. Apr.

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Children undergoing minor elective surgery at Ghent University Hospital

Description

Inclusion Criteria:

• Patient admitted to the operating room for minor elective surgery
• Patients undergoing general anesthesia for minor elective surgery
• Patient age: children from 2 years to 15 years
• Patients receiving cefazolin or paracetamol according to the standard procedure
• Intra-arterial (preferred) or intravenous access available for blood sampling
• BMI

Exclusion Criteria:

• Personal or family history of excessive bleeding
• Pre-existing coagulopathy and/or thrombocytopenia
• No catheter available for blood sampling
• Absence of parental consent
• Known allergy to one of the components of the study
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard of Care Paracetamol or Cefazolin treatment in children with normal weight	Drug: Cefazolin; Prophylactic Cefazolin treatment per standard-of-care; Other Names: Cephazolin; Drug: Paracetamol (drug); Preoperative dose of paracetamol, as per standard-of-care; Other Names: Acetaminophen
Standard of Care Paracetamol or Cefazolin treatment in children with overweight	Drug: Cefazolin; Prophylactic Cefazolin treatment per standard-of-care; Other Names: Cephazolin; Drug: Paracetamol (drug); Preoperative dose of paracetamol, as per standard-of-care; Other Names: Acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood concentrations of paracetamol and its metabolites	Blood concentrations (mg/L) of paracetamol and its metabolites: glucuronide-, sulfate-, cysteine- and mercapturate-conjugates after a single intravenous perfusion of paracetamol. Samples collected with Volumetric Absorptive Microsampling (VAMS).	Blood VAMS samples collected at day0 (D0): 1) before infusion(D0): predose , 2) 5 minutes after infusion (D0), 3) 5-120 minutes after infusion (D0): distribution phase, 4) 2 hours after infusion (D0), 5) 3-5 hours after infusion (D0): elimination phase
Cefazolin plasma and tissue concentrations	Plasma concentrations (mg/L) are stored in heparine blood tubes. Tissue concentrations (mg/L) are collected with a microdialysis device and stored in specific microdialysis vials.	At D0 sampled: Plasma: 1) predose, 2) 5 minutes after infusion, 3) 5-120 minutes, 4) 2 hours, 5) 3-5 hours; Microdialysis: 1) baseline (-30 - 0 minutes), 2) first 2 hours after dosing (every 30 minutes a sample), 3) next 3 hours (every 1 hour a sample)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers values: enzymes	Determination of the presence and concentration of enzymes based on the values Aspartate aminotransferase (AST; U/L), Alanine aminotransferase (ALT; U/L), and Gamma-Glutamyl transpeptidase (GGT; U/L).	Blood was collected togheter with blood sample 4 for cefazolin concentrations, 2 hours after drug administration on day0 (D0)
Biomarker values: proteins	Determination of the presence and concentration of proteins based on the values Bilirubin (total & direct; g/L), serum creatinine (SCR; g/L), total protein (g/L), Albumin (g/L), and C-reactive protein (CRP; g/L).	Blood was collected togheter with blood sample 4 for cefazolin concentrations, 2 hours after drug administration on day0 (D0)

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Study Director: Anca Amza, Ghent University Hospital and Ghent Univeristy

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2023
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Overweight; children; Paracetamol; Cefazolin
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; beta-Lactams; Lactams; Cephalosporins; Thiazines; Acetaminophen; Cefazolin; Pharmaceutical Preparations
• Other Study ID Numbers: ONZ-2023-0432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No