Pediatric pharmacotherapy

Common terms
• Children undergo considerable physiologic changes between birth and
adulthood.
Common Equations Used for Calculations in
Paediatric Patients
 Pediatric pharmacokinetics: absorption
oral

• Neonates gastric acid reduced to near neutral PH ( reaches adult value after 2-3 years)

- Absorption of acid label-labile drugs increased (pencilling G and erythromycin)

- Absorption of weak acid decreased (phenobarbital and phenytoin)

• Low splanchnic circulation

• Low enzyme and low intestinal drug metabolism

Intramuscular

- Absorption reduced muscle size, weaker muscle contractions, and an immature vasculature
resulting in more erratic blood flow to and from the muscle
 Absorption…cont
• subcutaneous administration, transdermal or percutaneous administration
results in greater drug absorption in neonates than it does in older children and
adults.
• Rectal administration is a useful route of drug delivery for many pediatric
patients
 Drug Distribution
• Extracellular fluid and total body water per kilogram of body weight are increased
in neonates and infants, resulting in higher Vd for water-soluble drugs, such as
aminoglycosides, and decreases with age
• Neonates and infants have a lower normal range for serum albumin (2–4 g/dL,
20–40 g/L), reaching adult levels after 1 year of age.
• Highly protein bound drugs, such as sulfamethoxazole-trimethoprim, are not
typically used in neonates due to theoretical concern for bilirubin displacement.
This displacement may result in a complication known as kernicterus, from
bilirubin encephalopathy
• Some medications (eg, vancomycin, phenobarbital) may also reach higher
concentrations in the central nervous system of neonates due to an immature
blood-brain barrier
 Metabolism and excretion

• Hepatic drug metabolism is slower at birth in full-term infants compared with

adolescents and adults, with further delay in premature neonate
• Nephrogenesis completes at approximately 36-week gestation
• premature neonates and infants have compromised glomerular and tubular
function that may correlate with a glomerular filtration rate (GFR)
• For example, vancomycin is often given every 18 to 24 hours in a low birth weight
(LBW) premature neonate, every 6 hours in children with normal renal function,
and every 8 to 12 hours in adult patients 
Formulations
• Infants and young children often require liquid formulations for oral
administration because they are unable to swallow solid (tablet and
capsule) dose forms and need doses based on body weight
• Challenge: Nearly three-fourths of the commercially available drugs in
the have not been labeled for use in infants and children.
Examples of Medications Not Available in a Liquid Formulation
IV drugs
• Intravenous drugs marketed for adult patients (but not labeled for
pediatric patients) are often too concentrated for accurate
measurement of small doses for newborn infants.
• For example, injectable morphine is available at 2 to 50 mg per mL
and phenobarbital at 30 to 130 mg per mL.
REASONS FOR LACK
OF DRUG FORMULATIONS
• additional costs
• limited financial returns,
• potential delay in marketing for adults
• and perceived greater legal liability and
• regulatory requirements are impediments to developing and
marketing a pediatric drug formulation
OPTIONS IN THE ABSENCE
OF DRUG FORMULATIONS
• When an appropriate formulation is not available, the options include
the following:
1. Refusing or delaying therapy with a potentially efficacious new drug
when the available drugs are not fully effective.
2. Calling the manufacturer for data on any extemporaneous
formulation.
3. Using an adult formulation somehow.
4. Preparing an extemporaneous formulation based on limited
PALATABILITY
• The child’s acceptance of a liquid dose form is primarily dependent on
its palatability.
• A better-tasting drug is easier to administer to infants and young
children, and thus loss of drug from spillage during dose
administration is minimized