Infants percutaneous drug absorption

Percutaneous drug absorption can present special problems in newborns, especially in preterm infants. While the skin of a newborn term infant may have the same protective capacity as the skin of an adult, a preterm infant will not have this protective barrier until after 2 to 3 weeks of life. Excessive percutaneous absorption has caused significant toxicity to preterm babies. Absorption of hexachlorophene soap used to bathe newborns has resulted in brain damage and death. Aniline dyes on hospital linen have caused cyanosis secondary to methemoglobinemia, and EMLA (lidocaine/prilocaine) cream may cause methemoglobinemia when administered to infants less than 3 months of age. 

Up to 40% of topically applied clioquinol can be absorbed percutaneously in man (20). Formulations that contain clioquinol are often used to treat diaper rash in a child of 10 kg treated with 1 g of clioquinol 3% tds, the amount of drug applied would be 9 mg/kg/day. However, it is possible that in infants with diaper rashes the actual absorption of the drug would be over 40%, since absorption through inflamed skin occurs more readily than through intact skin, and infant skin is more permeable than adult skin (21). 

Percutaneous absorption may be increased substantially in newborns because of an underdeveloped epidermal barrier (stratum comeum) and increased skin hydration. The increased permeability can produce toxic effects after the topical use of hexachlorophene soaps and powders, salicyhc acid ointment, and rubbing alcohol. Interestingly, a study has shown that a therapeutic serum concentration of theophylline can be achieved to control apnea in premature infants of less than 30 weeks gestation after a topical apphcation of gel containing a standard dose of theophylline. " The use of this route of administration may minimize the unpredictability of oral and intramuscular absorption and complications of intravenous drug administration for certain drugs. 

Children have a greater ratio of surface area to mass than adults, so a given amount of topical drug results in a greater systemic dose. Based on transepidermal water loss ami percutaneous absorption studies, term infants seem to possess a stratum comeum with barrier properties comparable with adults. 

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