Neonatal Pharmacokinetics and Drug Therapy: (1-13)
1.Gestational Age - # weeks after mothers last menstrual cycle
Postnatal Age - age after live birth
Preterm - <38 gestational weeks old
Term - 38 – 42 gestational weeks old
Neonate - <1 month of age after birth
2.ParameterNeonateInfantChild(+) prolonged, (-) reduced, (N) normal
Gastric acid production - N N
Gastric Emptying time + - -
Intestinal motilityirregularirregular N
Intestinal permeabilityimmatureimmature N
Intestinal surface area - ? N
Biliary function - N N
Microbial flora - N N
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.NeonateInfantAdult
Total Body Water70-80%60%50-60%
Fat Stores1-2%10-15%20-25%
Plasma Proteinless?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.PreemieNeonateInfantChildAdolescentAdult
Vd differsincreasedincreasedmidlowlowlowest
Normal Vd (L/kg)0.5 – 1.2 0.5 0.4 0.35 0.30.2-0.25
7.PreemieNeonateInfantChildAdult
Vd differsincreasedincreasedmidlowlowest
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 –glucuronidation, causes Gray Baby Syndrome
Acetaminophen - Sulfation, used till glucuronidation develops
Morphine - Sulfation, used till glucuronidation develops
Tetracyclineteeth 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 secretionlower at birth, reach adult values ~ 12 months
Reabsorptionlower 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.PreemieNeonateInfantChildAdolescentAdult
Vd Aminoglycosideincreasedincreasedmidlowlowlowest
Vd Phenytoinincreasedincreasedmidlow?lowest
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
Trough drawn within 1 hour prior to next dose
3.If trough to high:increase interval between doses (ie. q 8hr change to q 12 hr)
If trough to low:increase dose (ie. 25mg q 8hr change to 50mg q 8hr)
If high peak and trough:increase interval between doses (ie. q 8hr change to q 12 hr)
If high peak and low trough: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.