Oral absorption may be reduced in premature infants and neonates due to differences in gastric acid secretion and pancreatic and biliary function. Full-term neonates have a gastric pH of 6 to 8 at birth and pH 1 to 3 by 48 hours of age. Gastric acid output per kilogram is lower in premature infants and increases with age to adult levels by 6 11 12

months of age. Low gastric acid secretion can result in increased serum concentrations of weak bases and acid-labile medications, such as penicillin, and decreased serum concentrations of weak acid medications, such as phenobarbital, due to increased ionization. Additionally, gastric emptying time and intestinal transit time are delayed in premature infants, increasing drug contact time with the GI mucosa and 13

drug absorption. Diseases such as gastroesophageal reflux, respiratory distress syndrome, and congenital heart disease may further delay gastric emptying time. Pancreatic exocrine and biliary function are also reduced in newborns, with about 50% less secretion of amylase and lipase than adults, reaching adult values as early as the end of the first year and as late as 5 years of age. Deficiency in pancreatic secretions and bile salts results in decreased bioavailability of prodrug esters, such as erythromycin,

which requires solubilization or intraluminal hydrolysis. Due to limited data on oral bioavailability of medications in infants and children for newer agents, some drug dosing recommendations may be extrapolated from adult safety and efficacy studies and case reports.

Topical or percutaneous absorption in neonates and infants is increased due to a thinner stratum corneum, increased cutaneous perfusion, and greater body surface-to-weight ratio. Hence, application of topical medications should be limited to the smallest amount possible. Increased percutaneous absorption can lead to high serum concentrations of topically applied drugs such as corticosteroids, lidocaine, or chlorhex-idine, as well as inactive additives such as propylene glycol, potentially causing adverse effects.

Intramuscular absorption in premature and full-term infants can be erratic due to variable perfusion, poor muscle contraction, and decreased muscle mass compared to older patients.14 Intramuscular administration may be appropriate for some medications; however, use of this route of administration can be painful and is usually reserved when others (e.g., IV) are not accessible, such as initial doses of ampicillin and gentamicin for neonatal sepsis.

Rectal absorption can also be erratic and is not a commonly recommended route of administration if there are other routes available (e.g., oral). This route is useful in cases of severe nausea and vomiting or status epilepticus. For medications that undergo extensive first-pass metabolism, bioavailability increases as the blood supply bypasses the liver from the lower rectum directly to the inferior vena cava. Availability of rectal dosage forms varies, with acetaminophen suppositories and diazepam gel as examples of medications used by the rectal route in pediatric patients. Rectal use of oral medications or other dosage forms is based on limited studies and case reports.

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