Prednisolone disposition in steroid-dependent asthmatic children

Area of Science:

• Pharmacology
• Pediatrics
• Respiratory Medicine

Background:

• Steroid-dependent asthma in children often presents with highly variable prednisone requirements.
• Understanding the pharmacokinetics of prednisolone is crucial for optimizing treatment in pediatric asthma.

Purpose of the Study:

• To determine the pharmacokinetics of a 40-mg intravenous dose of prednisolone in children with steroid-dependent asthma.
• To investigate if pharmacokinetic parameters or protein binding explain variable prednisone responses in these children.

Main Methods:

• Measured plasma concentrations of prednisolone and cortisol over 24 hours using high-performance liquid chromatography.
• Assessed eosinophil counts and prednisolone's concentration-dependent protein binding.
• Calculated pharmacokinetic parameters including half-life, volume of distribution, and plasma clearance.

Main Results:

• Mean prednisolone half-life was 2.5 +/- 0.5 hr, volume of distribution was 52.8 +/- 14.5 L/1.73 m2, and plasma clearance was 246 +/- 62 ml/min/1.73 m2.
• Pharmacokinetic parameters, protein binding, and eosinopenic response were similar to healthy adults and steroid-dependent asthmatic adults.
• No significant differences were observed between responsive and resistant patient groups.

Conclusions:

• The pharmacokinetics and protein binding of prednisolone in children with steroid-dependent asthma are comparable to adults.
• These pharmacokinetic factors do not account for the wide variability in prednisone requirements and clinical responses observed in pediatric patients.