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Pharmacokinetics of rectal paracetamol after repeated dosing in children
T W Hahn1, S W Henneberg, R J Holm-Knudsen
1Department of Pharmaceutics, Royal Danish School of Pharmacy, Universitetsparken, Copenhagen, Denmark.
Insights
Saliva paracetamol levels correlate well with serum concentrations in children post-surgery. This study found no evidence of drug accumulation with the prescribed dosing regimen, supporting its safe use in pediatric patients.
Area of Science:
- Pediatric Pharmacology
- Clinical Pharmacokinetics
- Pain Management
Background:
- Post-operative pain management in children often involves paracetamol.
- Accurate monitoring of drug levels is crucial for efficacy and safety.
- Non-invasive methods for drug concentration measurement are desirable.
Purpose of the Study:
- To evaluate the correlation between serum and saliva paracetamol concentrations in pediatric patients.
- To assess the pharmacokinetic profile of paracetamol suppositories in children.
- To determine if the standard dosing regimen leads to drug accumulation.
Main Methods:
- Twenty-three children (9 weeks to 11 years) received paracetamol suppositories (25 mg/kg every 6 hours).
- Serum and saliva samples were collected for drug concentration analysis.
- Pharmacokinetic analysis was performed using a one-compartment linear model (ADAPT II).
Main Results:
- A strong positive correlation (r=0.91) was observed between saliva and serum paracetamol concentrations.
- Mean steady-state concentration was 15.2 mg/L, reached at approximately 11.4 hours.
- Body weight, age, and body surface area correlated significantly with clearance and volume of distribution.
Conclusions:
- Saliva paracetamol measurement is a reliable non-invasive method for monitoring therapeutic levels in children.
- The standard dosing regimen of paracetamol suppositories does not lead to supratherapeutic concentrations in pediatric patients.
- Pharmacokinetic parameters are influenced by patient demographics, aiding in personalized dosing.
Abstract:
Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P < 0.05) between saliva and serum concentrations. A one-compartment linear model with first-order elimination and absorption and lag-time was fitted to the data (ADAPT II). At steady state, the mean (SD) concentration was 15.2 (6.8) mg litre-1. Mean (SD) time to reach 90% of the steady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P < 0.05) with clearance and apparent volume of distribution. There was no evidence of accumulation leading to supratherapeutic concentrations during this dosing schedule for a mean of approximately 2-3 days.