pediatrics
Pharmacokinetics in Children
Absorption
Absorption from the gastrointestinal tractis affected by Gastric acid secretion Bile salt formation Gastric emptying time Intestinal motility Bowel length and effective absorptive surface Microbial flora Illness All these factors vary with age ( Absorption reference ). Reduced gastric acid secretion increases bioavailability of acid-labile drugs (eg, penicillin) and decreases bioavailability of weakly acidic drugs (eg,phenobarbital). Reduced bile salt formation decreases bioavailability of lipophilic drugs (eg,diazepam). Reduced gastric emptying and intestinal motility increase the time it takes to reach therapeutic concentrations when enteral drugs are given to infants<3 months old. Drug-metabolizing enzymes present in the intestines of young infants are another cause of reduced drug absorption. Infants with congenital atretic bowel or surgically removed bowel or who have jejunal feeding tubes may have specific absorptive defects depending on the length of bowel lost or bypassed and the location of the lost segment. How the type of food consumed may alter gastric emptying should also be considered (eg, solid versus liquid). Alterations in intestinal flora that aid metabolism may also affect absorption in the gut. Injected drugsare often erratically absorbed because of Variability in their chemical characteristics Differences in absorption by site of injection (intramuscular or subcutaneous) Variability in muscle mass among children Illness (eg, compromised circulatory status) Variability in depth of injection (too deep or too shallow) Intramuscular injections are generally avoided in children because of pain and the possibility of tissue damage, but, when needed, water-soluble drugs are best because they do not precipitate at the injection site. Transdermal absorptionmay be enhanced in neonates and young infants because the stratum corneum is thin and because the ratio of surface area to weight is much greater than for older children and adults. Skin disruptions (eg, abrasions, eczema, burns) increase absorption in children of any age. Transrectal drug therapyis generally appropriate only for emergencies when an IV route is not available (eg, use of rectaldiazepamfor status epilepticus). Site of placement of the drug within the rectal cavity may influence absorption because of the difference in venous drainage systems. Young infants may also expel the drug before significant absorption has occurred. Absorption ofinhaled drugsfrom the lungs (eg, beta-agonists for asthma, pulmonary surfactant for respiratory distress syndrome) may vary less by physiologic parameters and more by reliability of the delivery device and patient or caregiver technique. 