Population pharmacokinetics of caffeine in neonates and young infants

The population pharmacokinetics of caffeine were investigated in 60 neonates and young infants using data collected during routine therapeutic drug monitoring. Clearance was influenced by body weight and postnatal age, and increased in the presence of dexamethasone. No clinical factors were identified that influenced volume of distribution. The population pharmacokinetic parameter estimates were then tested prospectively in a further 20 neonates. Although they produced unbiased results, the dexamethasone effect could not be identified. A final analysis using all 80 patients found clearance (L/day) = 0.14 x weight (kg) + 0.0024 x postnatal age (days) (+/- 20%) and volume of distribution = 0.82 L (+/- 24%). Simulations based on these results indicated that the current dosage guidelines of 20 mg/kg loading dose of caffeine citrate followed by a 5 mg/kg/day maintenance dose should achieve concentrations within the traditional target range in > 70% of neonates.