IMM 31: Pediatric Pharmacokinetics Flashcards
1
Q
Oral Drug Absorption
A
- higher gastric pH – decreased absorption of ‘acidic’ drugs
- less peristalsis – slower gastric emptying
- reduced gastric motility – most drugs absorbed in small intestine, longer time to achieve max concentration (ie. acetaminophen)
- lack of intestinal flora – altered oral bioavailability of drugs (ie. digoxin)
- decreased first pass effect – approaches adult values at 6-12 months
2
Q
Rectal Absorption
A
- erratic absorption
- retention time
- bioavailability – depends on formulation used (solid vs. liquid)
- venous drainage for lower GI tract – superior rectum undergoes 1st pass metabolism, lower rectum bypasses portal circulation
- lipophilic drugs best PR absorption – ie. barbituate, benzodiazepine
3
Q
Percutaneous Drug Absorption
A
- larger BSA: body mass ratio
- better hydration and perfusion
- thinner stratum corneum – increased absorption of topical agents, too erratic for predictable drug delivery, potential for systemic toxicity
4
Q
Drug Absorption Summary
A
- erratic absorption
- prolonged drug exposure in stomach increases time to absorption and Cmax
5
Q
What is drug distribution influenced by?
A
- body composition and solubility of drug in water vs. fat
- protein binding
- body compartment sizes
- hemodynamic factors – cardiac output
- regional perfusion
- membrane permeability
6
Q
Body Composition
Premature Infant
- total body water
- ECF water
- fat
A
- total body water: 80-85%
- ECF water: 40-45%
- fat: < 5%
7
Q
Body Composition
Term Neonate
- total body water
- ECF water
- fat
A
- total body water: 75-80%
- ECF water: 45-55%
- fat: 10-15%
8
Q
Body Composition
6 months
- total body water
- ECF water
- fat
A
- total body water: 65-70%
- ECF water: 20-25%
- fat: 15-20%
9
Q
Body Composition
12 months
- total body water
- ECF water
- fat
A
- total body water: 60-65%
- ECF water: 18-20%
- fat: 20-25%
10
Q
Body Composition
Adolescents
- total body water
- ECF water
- fat
A
- total body water: 55-60%
- ECF water: 25-30%
- fat: 15-30%
11
Q
Protein Binding
A
- age at which protein binding reaches adult levels and function is unknown (approximately 1 year)
- clinical importance for drugs with 80-90% protein binding
- albumin concentration and binding capacity and affinity is lower at birth, and increases with age
12
Q
Protein Binding
What does a lower albumin concentration, binding capacity, and affinity mean for drugs?
A
reduced binding of ceftriaxone, penicillins, phenytoin, sulfa drugs
13
Q
Protein Binding
α1-acid glycoprotein
A
- neonates 33% of adult levels
- reduced binding of drugs such as lidocaine and propranolol
- reaches adult levels by 1 year of age
14
Q
Protein Binding
Bilirubin
A
- ↑ in neonates
- binds to albumin
- albumin has lower affinity for bilirubin than in adults
- many drugs displace bilirubin from albumin (higher binding affinity), resulting in kernicterus
15
Q
Membrane Permeability
What body sites is it difficult to penetrate?
A
- CNS – blood brain barrier
- eye
- sinuses
- lungs
- bones
- joints
16
Q
Distribution Summary
A
- higher fat in infants –↑ volume of distribution of lipophilic drugs (ie. sedatives, phenobarbital)
- larger proportion of ECF in neonates and
infants – ↑ volume of distribution of hydrophilic drugs (ie. aminoglycosides) - permeability of many membranes ↑ – ↑ Vd and penetration
