Neonatal Pharmacokinetics and Drug Therapy: (1-13)
1. Gestational Age Postnatal Age Preterm Term Neonate -
# weeks after mothers last menstrual cycle
age after live birth
<38 gestational weeks old
38 – 42 gestational weeks old
<1 month of age after birth
2. Parameter
Gastric acid production
Gastric Emptying time
Intestinal motility
Intestinal permeability
Intestinal surface area
Biliary function
Microbial flora
Neonate Infant
Child
N
N
+
irregular irregular
N
immature immature N
?
N
N
N
N
N
(+) prolonged, (-) reduced, (N) normal
3. Increased absorption through the skin compared to adults.
- increased BSA to body size ratio (3:1 neonate)
- thinner stratum corneum
- increased skin hydration
Iodine – thyroid dysfunction and abnormal growth
Hydrocortisone – can result in Cushing’s syndrome (hyperglycemia, hypertension, diabetes,
decreased bone growth, etc…)
4.
Total Body Water
Fat Stores
Plasma Protein
Neonate
70-80%
1-2%
less
Infant
60%
10-15%
?
Adult
50-60%
20-25%
normal
5. The staining and subsequent damage of the brain by bile pigment (bilirubin)
Caused by displacing bilirubin from albumin sites.
Drugs: sulfonamides & ceftriaxone
6.
Vd differs
Normal Vd (L/kg)
Preemie
increased
0.5 – 1.2
Neonate Infant
increased mid
0.5
0.4
Child
low
0.35
Adolescent Adult
low
lowest
0.3
0.2-0.25
Vd differs
Preemie
increased
Neonate Infant
increased mid
Child
low
Adult
lowest
7.
Neonates need a higher loading dose 15-20mg/kg vs adults 10-15mg/kg
8. Phase I Reactions Neonates:
Oxidation –
takes 2 - 4 weeks to get to adult values
Reduction –
present and fully functional
Hydrolysis –
takes 1 – 12 months to get adult values
Demethylation – reduced but present, takes 2 – 3 months till adult values
9. Phase II Neonates:
Glucuronidation – limited ability takes 6 – 18 till adult values
Sulfation –
present and fully functional
Glycination –
decreased but increases by 8 weeks
Methylation –
present and fully functional
Chloramphenicol –
Acetaminophen Morphine Tetracycline
glucuronidation, causes Gray Baby Syndrome
Sulfation, used till glucuronidation develops
Sulfation, used till glucuronidation develops
teeth can become permanently stained
10. Do not use for the first 2-6 months or it causes Gasping Syndrome.
Benzyl alcohol is a preservative used in some IVs. Cleared by Glycination.
99mg/kg is a toxic level.
11. Glomerular filtration – lower at birth, reach adult values ~ 5 months
Tubular secretion
lower at birth, reach adult values ~ 12 months
Reabsorption
lower at birth, increases with age
12. BSA to body size ratio is much higher than adults (3:1) so may get 3 times the level you
would in an adult which can be toxic.
13. Bacteremia
Systemic signs of infection (ie. temp)
Apnea
Poor feeding
Temperature instability
Lethargy
Principles of Pediatric Pharmacotherapy: (1-4)
1.
Preemie
Vd Aminoglycoside increased
Vd Phenytoin
increased
Neonate Infant
increased mid
increased mid
Child
low
low
2. Get levels after steady state has been reached.
Vancomycin: half-life ~ 6hr (ss about 4th dose)
Peak drawn 30 min after a 60 min infusion
Trough drawn within 1 hour prior to next dose
Aminoglycosides: half-life ~ 3 hrs (ss about 3rd dose)
Peak drawn 30 min after a 30 min infusion
Adolescent Adult
low
lowest
?
lowest
Trough drawn within 1 hour prior to next dose
3. If trough to high:
If trough to low:
If high peak and trough:
If high peak and low trough:
increase interval between doses (ie. q 8hr change to q 12 hr)
increase dose (ie. 25mg q 8hr change to 50mg q 8hr)
increase interval between doses (ie. q 8hr change to q 12 hr)
decrease dose and decrease interval (ie. 25mg q 8hr change to 15mg q 6hr)
Vancomycin Goal: Peak 20-40
Trough 5 - 15
Aminoglycoside Goal: Peak 6-8
Trough <2
4. Drug clearance is unpredictable in peds vs. adults, depending on the age of the child and drug they
may have increased clearance or decreased clearance.