This document discusses several important pharmacokinetic differences between pediatric patients and adults that are important to consider when prescribing medications to children. It notes that gastric acid production, digestive enzyme levels, and gastrointestinal absorption can vary significantly in infants and young children compared to adults. Metabolism and elimination pathways are also immature at birth and develop over time. These developmental differences mean that drug dosing often needs to be adjusted based on a child's age to ensure both efficacy and safety.

1. Pediatric Drug Use (1Pediatric Drug Use (1((
Prof Dr Hussein AbdeldayemProf Dr Hussein Abdeldayem
Professor of PediatricsProfessor of Pediatrics
Facebook/ Dayem PedoFacebook/ Dayem Pedo

2. Newborn and Infants areNewborn and Infants are
not young adultsnot young adults

3. Pharmacokinetic DifferencesPharmacokinetic Differences
GIT absorptionGIT absorption
 In the first two years ,gastric acid production isIn the first two years ,gastric acid production is
decreased, which results in basic drugs having betterdecreased, which results in basic drugs having better
absorption in the newborn and acidic drugs havingabsorption in the newborn and acidic drugs having
reduced absorptionreduced absorption
 The enzymes of digestion, such as bile acid andThe enzymes of digestion, such as bile acid and
pancreatic enzymes, are also lacking at birth and maypancreatic enzymes, are also lacking at birth and may
affect the absorption of acid sensitive agentsaffect the absorption of acid sensitive agents
 Less is known about changes between 2 and 18 years
of age
 All of these variables make it difficult to predict how theAll of these variables make it difficult to predict how the
GI absorption of a certain drug will be affectedGI absorption of a certain drug will be affected..

4. Increased phenobarbital absorption has been
shown in older pediatric patients, while
digoxin absorption is much less predictable
and consistent in children compared to adults.

5. Intramuscular and subcutaneous routesIntramuscular and subcutaneous routes
Infants and neonates have limited muscle mass and/orInfants and neonates have limited muscle mass and/or
fat stores, and their blood circulation is not alwaysfat stores, and their blood circulation is not always
mature.mature. All of these factors limit absorption by theAll of these factors limit absorption by the
intramuscular and subcutaneous routesintramuscular and subcutaneous routes..
The volume of injection to be injected intramuscularlyThe volume of injection to be injected intramuscularly
is limited in infants and neonates to 0.5 ml peris limited in infants and neonates to 0.5 ml per
dose in the lateral aspect of the thigh; grade schooldose in the lateral aspect of the thigh; grade school
age should not be given more than 1 mlage should not be given more than 1 ml
intramuscularly. Children more than 11 years canintramuscularly. Children more than 11 years can
receive up to 5 ml per dosereceive up to 5 ml per dose Pediatrics. 1998;102:428-430.Pediatrics. 1998;102:428-430.

6. Percutaneous absorption
 Is increased in neonates and infants. As a result of
thinner, more hydrated stratum, corneum and greater
skin surface area to body size ratio
 This results in potential toxicities from different
antiseptic agents such as
1-povidone iodine/alcohol which is used as a topical
disinfectant
2-suppression of the pituitary-adrenal axis after
prolonged use of topical steroid. Thus topical
application of hydrocortisone for diaper rash should
be limited to no longer than 2 weeks and only with
creams containing 0.5% cortisone or less ..

7. Rectal administration
 Is a valuable route for pediatric patients. It has a
predictable absorption for important medications that
may be needed in times when oral administration is
contraindicated or not practical
 Oral preparations of valproic acid, carbamazepine,
and some benzodiazepines can be given rectally in
seizing or vomiting patients with a high degree of
success

8. DistributionDistribution
Growth and maturation affect water content, fatGrowth and maturation affect water content, fat
content, hemodynamics, plasma proteincontent, hemodynamics, plasma protein
concentration, organ size, and tissue perfusionconcentration, organ size, and tissue perfusion
Total body water is high in neonates with rapid
reduction during the first year of life and
gradually reaching adult values by 12 years of
age -- leading to the need for higher doses of
hydrophilic drugs such as aminoglycosides .
Applied Therapeutics, 1992;10-1-10-32Applied Therapeutics, 1992;10-1-10-32

9.  Plasma protein concentrations Total protein
concentration at birth is only 80% of that of adults;
full adult values are achieved by 1 year of age
leading to more free drug and higher potential of
toxicity . It does not change appreciably between 2
and 18 years of age in healthy children
 Blood brain barrier is immature during the
newborn period - resulting in higher concentrations
within brain tissue.

11. MetabolismMetabolism
 With growth and maturation changes affect the bloodWith growth and maturation changes affect the blood
circulation to thecirculation to the liver and the hepatic enzymeliver and the hepatic enzyme
systems themselves. The total CYP content in the fetalsystems themselves. The total CYP content in the fetal
liver is estimated to be half that of the adult. thisliver is estimated to be half that of the adult. this
explains the very long half-life ofexplains the very long half-life of caffeinecaffeine andand
theophyllinetheophylline in this group of patientsin this group of patients
 CYP matures by 4-6 months of age and, by thatCYP matures by 4-6 months of age and, by that
time, it may exceed the activity of that of adults on atime, it may exceed the activity of that of adults on a
mg per kg basismg per kg basis
 Gray baby syndrome has been caused byGray baby syndrome has been caused by
chloramphenicolchloramphenicol within the recommended dosagewithin the recommended dosage
range. This has been shown to be due to therange. This has been shown to be due to the
deficiency of glucouronidation in neonates anddeficiency of glucouronidation in neonates and
infantsinfants

12. There is also substantial inter-patient
variability in the activity of these pathways for
children of the same age. This may translate
into 2- to 3-fold variability in the systemic
clearance of some drugs, even in children with
no underlying pathophysiology that might
affect drug disposition. In addition, some
pathways may be completely absent in a
subset of individuals as a result of a genetic
defect Applied Therapeutics, 1992;7-1-7-32

13. EliminationElimination
 Renal function increases over the first year of life, but
it is essentially at adult (corrected for body size) level
by the age of 1 year and remains constant over the
pediatric and adolescent age range, as shown in Thus,
there is no general age-related change in renal
function over this age period
 For example, the ampicillin dose in the first week of
life is 50 mg/kg every 12 hours, but after the first
week, it should be adjusted to 50 mg every 8 hours

15. Pharmacodynamic differences in pediatricPharmacodynamic differences in pediatric
populationpopulation
 There has been little work done on the drug receptor
differences in pediatrics. Based on animal studies, it
has been suggested that receptor function begins to
develop in the fetal stage and matures to full function
long after birth. More research in this area is
warranted.

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