Variability In Pediatrics - testable Content

• Infants and children have

  • Thinner epidermal layer

  • More/higher epidermal hydration

  • Greater perfusion of Subcutaneous layer

  • Immature barrier function

  • AKS (INCREASED ABSORPTION!!!!)

For topical absorption of drugs in children,

little water bags; Volume of Distribution; hydrophilic; GIVE MORE DRUG ON A WEIGHT BASED SCALE - still proportional though for children

babies/Infants are _______ and have increased _____ which makes it easier for _____ drugs versus lipophilic, SO we must _____

• Lower Binding capacity to protein

• Competing substrates (like Bilirubin or FFA)

• Decreased Affinity

• Fewer plasma proteins

Components of Protein distribution in Children

• More unbound drug free in plasma = Higher toxicity risk! 

• Differences in Vd

• Displacement of bilirubin from protein (kernicterus)

• Increased permeability of the BBB

Additional Protein distribution points for children

• Responsible for 15% of drugs eliminated by metabolism

• Neonates and infants may use other pathways until UGT is developed

• Starts functioning ~ 2 months old, and adult levels are reached at age 1

For children and infants, the Phase II enzyme UGT is: 

• Is responsible for sulfation

• Has HIGH activity, but lower capacity at birth

For children and infants, the phase II enzyme SULT: 

• is responsible for acetylation

For children and infants, the phase II enzyme NAT: 

Elimination!!!

The biggest PK issue that children/infants have IS

• Kidneys are immature at birth in structure and function

• They DO NOT effectively concentrate urine until about 1 year of age

• Electrolyte secretion and absorption are not optimally controlled, and are at risk for dehydration

Issues with kidney function in infants/Children in regard to PK

• renal blood flow increases during the first year of life

• Results in EXTENDED half-lives of really eliminated drugs

Other problems with kidney function in infants/Children in regard to PK

(0.41 x height (cm)) / SCr

The Bedside Schwartz Equation for renal function estimation in children

Children (after 1-2 YO) > Adults > Neonates

The renal function comparison of adults, children, and neonates