Developmental Aspects of Percutaneous Caffeine Absorption in Premature Infants

Abstract

Caffeine is commonly used in the treatment of apnea of prematurity. The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in low birthweight infants (less than 1500 gm) with gestational age between 26 and 34 weeks, a group of 56 preterm babies was studied after percutaneous application of 7.5 mg twice daily of caffeine for babies with birthweight less than 1000 gm and 10 mg twice daily for babies with birthweight more than 1000 gm. The reported technique is a useful alternative method of drug administration in premature babies. This study indicates an inverse relationship between gestational age and skin absorption contributing to a better understanding of skin barrier function in the newborn.

Development of an in vitro model for premature neonatal skin: Biophysical characterization using transepidermal water loss

“…The coincidence between the premature neonate data and the in vitro porcine skin results in Figure 3 suggests that the latter can be tape‐stripped to a level that corresponds to a particular barrier maturity in vivo . This would then offer a tool with which to explore the potential of transdermal drug delivery to this unique patient population, the barrier of which is an unusual “moving target.” It has already been shown in the literature (Rougier et al, 1999) that a less than perfect SC (across which TEWL is elevated) is a more permeable barrier to drug permeation,29 and it has been clearly demonstrated that the delivery of drugs across premature neonatal skins depends on the PCA 17,30–34. Clearly, the logical step now is to show that the biophysically established correlation derived here can be extended and applied usefully to the prediction and quantification of transdermal drug delivery.…”

Effective use of transdermal drug delivery in children

“…Similarly, the application of a different caffeine gel to 56 preterm (26-34 wk GA) infants produced systemic levels which increased from day 2 to day 10 of treatment, reaching therapeutic efficacy in 48 h [58]. Serum concentrations were better correlated to gestational age than birth weight; high drug levels, although without side effects, were measured for the most immature patients.…”

Considerations in the Rational Design and Conduct of Phase I/II Pediatric Clinical Trials: Avoiding the Problems and Pitfalls

“…[24][25][26][27][28] Transdermal formulations may be more efficiently delivered in preterm neonates owing to a decrease in stratum corneum thickness and in fullterm neonates and young infants owing to improved hydration properties of the skin and a larger surface to volume ratio. [29][30][31][32] As it relates to administering medications, sponsors need to maintain realistic expectations in the design and conduct of their pediatric clinical trial. In a single-dose study, it may be feasible to circumvent the need for a pediatric formulation by ensuring that the child can swallow a placebo; however, this does not ensure that accurate delivery can be sustained when protracted administration regimens are required (e.g., multiple-dose investigations).…”

“…In addition to being poorly accepted by older children, rectal formulations may be evacuated more quickly in younger children owing to an increase in the frequency high‐amplitude pulsatile contractions of the lower intestinal tract 24 , 25 , 26 , 27 , 28 . Transdermal formulations may be more efficiently delivered in preterm neonates owing to a decrease in stratum corneum thickness and in full‐term neonates and young infants owing to improved hydration properties of the skin and a larger surface to volume ratio 29 , 30 , 31 , 32…”