[Relation between dose, plasma concentration and therapeutic effect of theophylline in children with sleep apnea]

Area of Science:

• Pediatric Pharmacology
• Neonatal Medicine
• Clinical Pharmacokinetics

Context:

• Infantile sleep apnea poses a significant risk to neonates.
• Theophylline is a potential therapeutic agent for managing apneic episodes in infants.
• Understanding theophylline pharmacokinetics in neonates is crucial for safe and effective dosing.

Purpose:

• To determine theophylline plasma concentrations in infants with sleep apnea.
• To correlate these concentrations with dosage, therapeutic response, and adverse effects.
• To establish pharmacokinetic parameters, including half-life (t 1/2) and clearance (Clss).

Summary:

• Twelve infants with infantile sleep apnea received an oral theophylline dose of 4 mg/kg/24 h.
• Plasma theophylline concentrations were measured using an enzyme immunoassay technique (EMIT).
• A weak correlation (r = 0.45) was observed between dosage and plasma concentration, likely due to clearance variations.
• Achieved concentrations (3.0–12.6 µg/mL) effectively controlled apnea without significant adverse effects, with only one infant showing mild irritability.
• Mean half-life was 13.30 ± 7.46 hours and mean clearance was 36.64 ± 12.98 mL/h/kg.

Impact:

• The study demonstrates that theophylline can be safely and effectively used to manage infantile sleep apnea.
• Established pharmacokinetic data (t 1/2, Clss) provide valuable insights for neonatal theophylline therapy.
• The findings suggest that two-sample pharmacokinetic analysis is reliable in this population, simplifying monitoring.
• Results align with existing literature, reinforcing theophylline's role in neonatal respiratory care.