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What are the pediatric differences in absorption that influence pharmacokinetics?
- Low gastric pH until 2 yr (effects penicillin, ampicillin)
- Delayed gastric emptying until 6-8 mo
- ↓ bile acids and pancreatic enzymes until 3 mo (effects clindamycin and chloramphenicol)
- IM inj not preferred (low blood flow and muscle mass)
What are the pediatric differences in distribution that influence pharmacokinetics?
- Higher water content and lower body fat than adults → larger VD for hydrophilic drugs (AG, Vanco)
- ↓ PPB → kernicterus risk from drugs that compete with bilirubin for binding (sulfonamides and Ceftriaxone)
- BBB more permeable (AG, Vanco)
- RBC membrane more permeable (ribavirin, 5-flucytosine) allows for more SE such as anemia d/t drug-enduced cell lysis
What are the pediatric differences in metabolism that influence pharmacokinetics?
- Limited glucuronidation ability until 3-4yo → gray baby syndrome from chloramphenicol
- Sulfation and methylation are well developed in neonates (used to metabolize APAP in neonates)
- Low alcohol dehydrogenase activity until 5yo:
- trouble metabolizing benzyl alcohol
- ↑ risk of disulfiram rxn with metronidazole when administered with alcohol-containing products
What are the pediatric differences in elimination that influence pharmacokinetics?
- maturity by 3yo
- low until 36wks gestation, then increase in first couple weeks after birth
- Big increase in tubular secretion after birth (affects pens and cephs)
- Can use urine output as indicator of renal fxn (at least 1 mL/kg/hr is normal)
- Can estimate CrCl if have two serum drug concentrations (eg AG)
- CrCl equations:
- Schwartz for 6 mo-21yo
- Traub and Johnson for 1-18yo
- Shull for 1-18yo
What are the major differences in pharmacokinetics between children and adults for aminoglycosides and Vancomycin?
- Larger VD → need a higher dose/kg to obtain the same concentrations as adults
- Higher clearance in children and adolescents
- Lower clearance in neonates and infants → need less frequent dosing
Why should Sulfonamides be avoided in pediatric patients?
- Highly PPB normally (In neonates, displaces bilirubin → ↑ risk of kericterus)
- CI until >2mo
Why should Ceftriaxone be avoided in pediatric patients?
Highly PPB normally. In neonates, displaces bilirubin → ↑ risk of kericterus CI until >2mo
Why should Chloramphenicol be avoided in pediatric patients?
- Immature glucuronyl transferase → gray baby syndrome
- Avoid until at least 3yo
Why should TCNs by avoided in pediatric patients?
- Teeth discoloration, altered bone development and growth
- Avoid until at least 8yo
Why should FQ be avoided in pediatric patients?
- Cartilage malformations in animal studies
- Not approved for < 18yo except for complicated UTIs in >1yo
Why should nitrofurantoin be avoided in pediatric patients?
- Immature RBC production and ↑ sensitivity to damage → hemolytic anemia
- CI until > 1mo