Pediatrics involves the care of infants, children, and adolescents. Knowledge of appropriate pharmacokinetics and pharmacodynamics in pediatric patients is lacking due to ethical issues in clinical trials. Dosages must account for the rapid physiological changes that occur during development, including variations in absorption, distribution, metabolism, and excretion of drugs across the different pediatric age groups. Careful dosage calculation based on body weight or surface area is necessary to ensure drug safety and efficacy in children.

1. PRESCRIBING IN

2. OUTLINES
• Introduction
• Pharmacokinetics
• Pharmacodynamics
• Pediatrics dosage and forms
• Medication Errors
• Summary
• Take home message

3. Introduction
• Paediatrics is a branch of medicine that deals
with the development, care and diseases of
infants, children and adolescents.
• Pediatric population is divided into:
-Preterm newborn (<37weeks GA)
-Term newborn (0-28 days)
-Infant (>28days-12 months)

4. Introduction
-Toddler (>12months-23months)
-Children(2-11years)
+Preschool (2-5years)
+School Aged(6-11 years)
-Adolescent(12-18years)

5. Introduction
• Knowledge about appropriate
pharmacokinetics and pharmacodynamics
effects in pediatrics is lacking.
• This is due to limited clinical trials conducted
because of ethical issues, lack of true
informed consent, number of blood samples
needed as well as rapid growth and
development of each stage of pediatric group.

6. Why is Paediatrics a special group??
GROUP SPECIAL FEATURES
PRETERM SMALL GESTATION AGE
UNIQUE ORGAN SUSCEPTIBILITY TO TOXICITY
TERM
NEONATES
IMMATURE ORGANS
AFFECTS MOST OF PHARMACOKINETICS
PARAMETERS
INFANTS RAPID PHYSIOLOGIC CHANGE IN TOTAL BODY
WATER,RENAL AND HEPATIC FUNCTIONS

7. Why is paediatrics special….
GROUP SPECIAL FEAUTURE
TODDLER CNS MATURATION OCCURS
INCREASED METABOLISM AND EXCRETION
CHILDREN ACCELERATED SKELETAL GROWTH,WEIGHT
GAIN AND PSYCHOMOTOR DEVELOPMENT
ADOLESCENTS ONSET OF PUBERTY AND SEXUAL
MATURATION

8. Pharmacokinetics
Absorption
GI factors affecting absorption
 Slow release of gastric acid during first few days
of life hence increased bioavailability of acid
labile drugs eg penicillin
 Prolonged gastric emptying time in newborns
this delays absorption.

9. GI factors affecting absorption….
 Intestinal motility is irregular and depends of
feeding patterns in newborns.
 Absorption of lipid soluble drugs is reduced
due to low concentration of lipase and bile
acids.

10. PHYSIOLOGIC
VARIABLES
NEWBORNS INFANTS CHILDREN
GASTRIC PH Neutral at birth up
to 1 hour
Adult values
at 3 months
Adult values
GASTRIC
EMPTYING
Prolonged Adult values
at 6-8 months
Decreased
INTESTINAL
MOTILITY
Decreased,
irregular
Increased Increased
GASTROINTESTI
NAL ENZYMES
ACTIVITIES
Lower Amylase,
Lipase,bile acid
activities( lipid
drugs absorption)
Developed at
4 months
Developed
MICROBIAL
FLORA
Colonization phase Adult pattern Adult pattern

12. Other factors affecting absorption
1:Absorption via IM and SC route is unpredictable
due to low skeletal mass and fat proportion of
newborns.
2:Perfusion to the administration area affects
absorption example preterm have less perfusion
in the muscles so drugs are absorbed slower.
3:Excessive percutaneous absorption due to skin
enhanced transdermal permeability and larger
surface area to volume ratio(systemic toxicity)

13. DISTRIBUTION
• As body composition changes with
development, the distribution volumes of drugs
are also changed.
• Factors affecting distribution of the drugs are:
1: High total body water content and low fat.
2:Reduced plasma protein content and binding
affinity
3:Immature brain blood barrier allowing drugs
to cross to CNS

14. DISTRIBUTION…
FACTOR PHYSIOLOGICAL
CHANGE
EFFECT
PLASMA
PROTEINS
SR ALBUMIN, α-ACID
GLYCOPROTEIN AND
OTHERS HAVE LOWER
CONC IN BIRTH AND
INFANCY
INCREASED CONC OF
PLASMA UNBOUND
DRUGS
(DIAZEPAM,PENICCILIN,
PHENOBARBITONE AND
PHENYTOIN)
BODY WATER
COMPOSITION
PRETERM(85%)
NEONATES(70-75%)
COMPARED TO ADULTS
(50-60%)
ENHANCE
DISTRIBUTION(VD) FOR
WATER SOLUBLE DRUGS
(AMINOGLYCOSIDES )

15. DISTRIBUTION…..
FACTOR PHYSIOLOGIC CHANGE EFFECT
BODY FAT
COMPOSITION
PRETERM 1% OF T.BODY
WEIGHT(TBW)
TERM 15% OF TBW
LOWER COMPAIRED TO
ADULTS
ORGANS WHICH
ACCUMULATE HIGH CONC
OF LIPID SOULUBLE
DRUGS WILL
ACCUMULATE LESS
HENCE DRUGS WILL BE
WELL DISTRIBUTED
BLOOD BRAIN
BARRIER(BBB)
IMMATURE BBB AND
HENCE HAVE INCREASED
PERMEABILITY TO DRUGS
DRUGS CAN CROSS BBB
AND CAUSE CNS EFFECTS

17. Metabolism of Drugs
The drug-metabolizing enzymes are immature
and lower capacity wise eg of CYP450 (50–70%
of adult value) during neonate period.
Slow clearance rates and prolonged elimination
half-lives during neonatal period because of
decreased metabolizing rate of the drugs.
During toddlerhood , the metabolic rate of
many drugs exceeds adult values, often
necessitating larger doses per kilogram than
later in life.

18. Metabolism of Drugs….
• Phase 1 (oxidation, hydrolysis, reduction)
a. Activity low at birth
b. Activity in young children exceeds adult
levels
c. Mature at variable rates
- Oxidative metabolism increases
rapidly after birth
- Alcohol dehydrogenase reaches
adult levels at five years

19. Metabolism of Drugs…….
• Phase 2 (conjugation, acetylation)
a) Conjugation:
-glucuronidation decrease at
birth,matures at age 3-4 years
-sulfatation increase at birth
b)Acetylation decrease at birth

20. Drug Excretion
• Renal function is limited at birth because the
kidneys are anatomically and functionally
immature leading to low GFR.
• In full-term newborns, glomerular filtration
rate (GFR) is 10–15 mL/min/m2, and in
premature infants the GFR is only 5–10
mL/min/m2.

21. Drug Excretion……
• GFR doubles by 1 week of age and reaches
adult values by 1 year of age
• Therefore, drugs that depend on renal
function for elimination are cleared very
slowly and should be given with caution eg
Gentamicin and ampicillin

22. Drug Excretion……
• Toddlers may have shorter elimination half-
lives of drugs than older children and adults.
• This is due to increased renal elimination rate
and increased metabolism

23. Comparison of elimination half-lives of
various drugs in neonates and adults.

24. Pharmacodynamics
• Response of drugs may be different because of
immature receptors or neurotransmitters.
• Neonates are also more sensitive to the central
depressant effects of opioids than are older
children and adults
• Administration of indomethacin causes the rapid
closure of a patent ductus arteriosus,
• Infusion of prostaglandin E 1 , on the other hand,
causes the ductus to remain open

25. Age related maturation of systems
ORGAN/PHYSIOLOGICAL
FEATURE
AGE OF MATURATION
Gastric acid production 3 months
Gastric emptying 6-8 months
Phase I enzyme reactions 5months-5 years
Phase II enzyme reactions 3-6 months
Glomerular filtration 3-5 months
Tubular secretion 6-9 months
Renal blood flow 5-12 months

26. Prescribing in Adolescents
Challenges fall into
1. Medicine safety and efficacy(Physiology of
puberty) eg long term use of corticosteroids
can affect growth
2. Flactuations in Adherence(chronic illness eg
DM)

27. Drug Dosage
Pediatric doses are
calculated by;
1:Body weight
–Measured in mg
per kg, mcg per kg
etc.
2:Body surface area
–Measured in m²

28. Dosage calculations
Young’s Rule:(based on age if weight is unknown)
Pediatric dose=
𝐴𝑔𝑒×𝐴𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
𝐴𝑔𝑒+12
Fried’s Rule: (age adjustment for infants)
Infant dose=
𝐴𝑔𝑒 ×𝐴𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
150

29. Dosage calculations
• Clark’s Rule: (based on body weight age 2-17y)
Pediatric dose =
𝑊𝑒𝑖𝑔ℎ𝑡 ×𝐴𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
150
• Best way to get the dose is by weight or
surface area of the child
Eg Iv Ceftriaxone 50-100mg/kg od(Infections)
Iv Vincristine 1.5mg/m2 (ALL)

30. Medication Errors
• Pediatric medication orders are prone to errors
than adult orders because;
-Doses are not standard
-Math errors can occur when calculating the
dose
-Suspensions often have to be compounded
-Tablets may have to be cut eg Ciprofloxacin
-Dilutions need to be made to make amounts
that are measurable

31. Summary
• There are six age groups to consider and various
factors and considerations to take into account as
regards each group
• The pharmacokinetics and pharmacodynamics,
despite not being too well studied, have effects on
drug action and must be considered.
• Dosages of drugs must be adjusted based on body
surface area / body weight
• Choose safer, rational and most effective drugs for
therapy.

32. Take home message
Determining how to give medications to
children involves an understanding of various
physiologic changes that occur during growth
and development.
Children are not small adults, drug dose
calculation is of paramount importance to
ensure safety and proper therapeutics effect.

33. References
• https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC6370610/