Evaluation of transdermal theophylline pharmacokinetics in neonates

Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.