This document provides an overview of principles of neonatal and pediatric pharmacology. It discusses pediatric ages and developmental stages. It then covers topics of pediatric pharmacokinetics including absorption, distribution, metabolism and excretion. Factors such as organ maturation, body composition and plasma protein binding affect how drugs are processed in pediatric patients compared to adults. The document also reviews monitoring parameters and considerations for pediatric drug therapy including dose calculations, choice of formulations, disease conditions, adverse reactions and counseling.

1. Principles of
Neonatal &
Pediatric
Pharmacology
Prepared by Zerin Sabah, Dunya Ahmed, Sliva Moayad,
Aydin Ibrahim, Jarin Sagvan
Supervised by Dr. Hishyar and Dr. Hussein

2. • Background
• Pediatric Ages
Introduction
• Absorbtion
• Distribution
• Metabolism
• Excretion
Peidatric Pharmacokinetics
• Vital signs
• Biochemical parameters
Monitoring Paramters
• Pediatric drug Therapy
• Dose Calculation
• Adverse Reaction
Peidatric Dosage

3. Introduction

4. Introduction
 Pharmacokinetics and Pharmacodynamics data are seldom avaible
o have not undergone specific pre-marketing clinical studies in children
 Data on therapheutic dosing for children
o based on case reports or very small population studies
o observations of usually unscientific observers
 Surface area, weight and age are common methods currently avaible to
predict paediatric therapheutic doses from those used for adults
 Special challenge
o constantly changing physiological and developmental status

5. Introduction
Normal length 37 - 42 weeks
Preterm <37 weeks gestational age
Post-term >42 weeks gestational age
Neonatal period Up to 28th day
Infant 1-12 months
Toddler 1-4 years
Children 4-12 years
Adolescent 12-18 years

6. Pharmacokinetics

7. Drug Absorption
Routes of Drug Absorption
1. Oral route
o pH dependent passive diffusion
o Gastric emptying time
o Peristaltic movement
o GI enzyme activitys
o Disease state
 In neonate irregular in any newborn baby and unavailable in the ill baby
 In older infants and children orally administered drug will be absorbed
at a rate and extent similar to those in healthy adults
Routes of
Drug Delivery
Oral
IM
IV
Topical
Rectal
Buccal

8. Drug Absorption
2. Intramuscular route
o avoided in premature babies because of their small muscle bulk.
o In infants and children the absorption is faster than in the neonatal period since
the muscle blood flow is increased
3. Topical route
o Premature infants have underdeveloped epidermal barrier (stratum corneum)
 Lead to poor barrier to water and highly permeability to substances
o Infants have increase in permeability of skin
 this will increase topical drug absorption

9. Drug Absorption
4. Intravenous route
o Absorption is complete 100% (maximum bioavailability)
5. Rectal Route
o Useful in patients who are vomitting or unable to take oral medication
o Rectal absorption probably similar to upper GIT
 But different PH, surface area and fluid content
6. Buccal Route
o Useful in patients who are vomitting or unable to take oral medication
o In neonate adminstration of glucose gel in treatment of hypoglycaemia

10. Drug Distribution - Review
 Reversible transport of drug by bloodstream to ist site of action
 Compartments for Distribution:
o Intracellular 40% Extracellular (Plasma 4%, Interstitial fluid 15%, Transcellular fluid 1%)
 Factors affect Distribution
o Blood flow, Permeability, Transport mechanism, Plasma proteins
 Volume of Distribution
o Vd = D/C -> C = D/Vd, as smaller Vd as larger the concentration
 Compartment Models
 Redistribution

11. Drug Distribution
80
70
61.2 64.8 64.4 60
54
12
13.4
13.4
17.3 18.1
16.5
12
6
13.4
22.4
13.7 13
18
30
2 3.2 3 4.2 4.3 5.5 4
0
10
20
30
40
50
60
70
80
90
100
Premature Full term 1 year 10 years 15 years Adult Eldery
Body Composition
Water Protein Fat Mineral

12. Drug Distribution
 The volume of distribution of drugs changes in children due to changes in body
composition and plasma protein binding through growth and development
1. Body water
o In younger children higher percentage of body weight is water
 Higher doses of water-soluble drugs are required in younger children
 Lower doses are required to avoid toxicity as children grow older
2. Body fat
o Amount of adipose tissue vary in different babys
 In general neonate, especially pre term, have less fat
 Lipid soluble drugs are not accumulated at fat reservoir
 Faster half-life elimination

13. Body Distribution
3. Plasma proteins
o Protein binding is lower because
1. Albumin and total protein concentrations are lower in neonates until 1 year
2. qualitative differences in binding proteins
3. competitive binding by molecules such as bilirubin and free fatty acids,
which circulate in higher concentrations in neonates and infants
 result may be
1. increased free drug concentrations
2. greater drug availability at receptor sites
3. Higher pharmacologic effects and adverse effects at lower drug concentrations

14. Drug Metabolism - Review
 Location
o Occurs primarily in the liver
o additional biotransformation occurs in the intestine, lung, kidney, adrenal gland and skin
 In liver, metabolism involves:
o Phase I reactions (Non Synthetic reactions)
o Phase II reactions ( Synthetic reactions)
 Phase I reactions
o Oxidation, reduction, hydrolysis
o Cytochrome family enzymes
 Phase II reactions
o Glucuronidation, sulfation, acetylation, glutathione conjugation

15. Drug Metabolism
 Depends greatly on the maturation level of the pediatrics patient and varies
from child to child.
 For most children younger than 2 years:
o Sustained decrease in levels of hepatic enzymes result in slower metabolism of
medications.
o Hepatic metabolic activity is lower in neonates, infant hepatic function matures at
age 1 to 2 months.
 Pediatric patients generally have higher metabolic rates than adults.
o Which courses the metabolism of medications to occur more rapidly
o Often necessitates a higher medication requirement than with adults

16. Drug Excretion - Review
 occurs in the kidneys, liver, intestine, lungs,
sweat, salivary and mammary glands
 Kidney is the major route of elimination for
o water soluble drugs
o water soluble metabolites of lipid soluble drugs
 The basic processes in renal elimination
1) Glomerular filtration
2) Tubular function

17. Drug Excretion
1) Glomerular filtration
o Premature infants have reduced filtration rates due to incomplete nephrogenesis
• 30% - 50% of adult value in full term neonates
• 85% adult values by 3-5 months of age
• 100% adult values by 6-12 months of age
2) Tubular function
o In infants tubular secretion rates are approximately 20%
o Does not achieve adult values until 6-7 months of age
o In neonates tubular reabsorption is decreased

18. Absorption
Distribution
Metabolism
Elimination

19. Monitoring parameters

20. Monitoring parameters
 It give an idea about therapy management in prolonged treatment
 Pediatric vital signs, Biochemical and Hematology parameters change
through childhood
Vital Signs
PARAMETERS AGE 2-5 AGE 5-12
Heart rate (beats/min) 100-120 80-100
Systolic blood pressure (mmHg) 80-90 90-110
Respiratory rates (beats/min) 25-30 16-25

21. Monitoring parameters
Biochemical and Hematologic Parameter
PARAMETERS AGE 2-5 AGE 5-12
Albumin (g/L) 30-50 35-55
Bilurubin (microM/L) <15 <17
Creatinine (microM/L) 30-80 50-120
Hemoglobin (g/dL) 11-14 Male: 13.5-18
Female: 12-16
WBC (x 109
/L ) 5-14 3.5-11

22. Pediatric Drug Therapy

23. Pediatric Drug Therapy
 a general term for using medication to treat disease
1. Dose Calculation
o Depends on age, weight and surface area
2. Choice of Dosage form
o Depends on choice of route of absorption
3. Disease Condition
o Liver, Kidney and Lung disease
4. Adverse Reaction
o Not cleared, but some well known
5. Counseling
o Concordence and adherence of both parents

24. Dose Calculation
 Clarks Rule
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑐ℎ𝑖𝑙𝑑 (𝑖𝑛 𝑝𝑜𝑢𝑛𝑑𝑠)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑤𝑒𝑖𝑔ℎ𝑡 (150 𝐼𝑏𝑠)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Frieds Rule
𝑎𝑔𝑒 (𝑖𝑛 𝑚𝑜𝑛𝑡ℎ)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑤𝑒𝑖𝑔ℎ𝑡 (150 𝐼𝑏𝑠)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Youngs Rule
𝑎𝑔𝑒 (𝑖𝑛 𝑦𝑒𝑎𝑟𝑠)
𝑎𝑔𝑒+12
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Catzel Rule
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎 𝑜𝑓 𝑐ℎ𝑖𝑙𝑑 (𝑖𝑛 𝑚2)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑠𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒 (1.76𝑚 2)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒

25. Adverse Reaction
 Mechanism is not cleared in adverse effect of many drugs in child#
o may be due to immature kinetic parameters and some medication errors
 Some well known adverse effect
•Teeth brown coloration
Tetracycline
•Growth suppression in Prepubertal
childCorticosteroids
•Paradoxical hyperactivity in child
Phenobarbital drugs
• Reye’s syndrom
Aspirin

26. Resources
 Websites
o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341411/
o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857037/
o http://www.merckmanuals.com/professional/pediatrics/principles-of-drug-treatment-in-
children/pharmacokinetics-in-children
 Videos
o https://www.youtube.com/watch?v=fM1J6rYCx38
o https://www.youtube.com/watch?v=kXQzyook0v8
o https://www.youtube.com/watch?v=Q2CX36XhMj0
 Books
o Sumner J. Yaffe Neonatal and Pediatric Pharmacology:
Therapeutic Principles in Practice 2010
o Roker Walker and Cate Whittlesea Clinical Pharmacy and Therapheutics:
Fifth Edition 2012
 Other
o Dr Hisyhar Lectures on Pharmacokinetics 2017