1. Drug Therapy in Pediatric Patients
Chapter 10
Drug Therapy in Pediatric Patients 1

2. Pediatric Patients All patients younger than16 years
Respond differently to drugs than the rest of the population
More sensitive to drugs than other patients are
Show greater individual variation
Sensitivity due mainly to organ system immaturity
Increased risk for adverse drug reaction 2

3. Pediatric Patients Ongoing growth and development
Different age groups: different challenges
Two-thirds of drugs used in pediatrics have never been tested in pediatrics.
Two laws
Best Pharmaceuticals for Children Act—2002
Pediatric Research Equity Act of 2003 3

4. Pediatric Patients
20% of drugs were ineffective in children even though they were effective in adults.
30% of drugs caused unanticipated side effects, some of them potentially lethal.
20% required dosages different from those that had been extrapolated from dosages used in adults. 4

5. Pediatric Patients Premature infants Full-term infants Neonates
(less than 36 weeks’ gestational age)
Premature infants
(36–40 weeks’ gestational age)
Full-term infants
(first 4 postnatal weeks)
Neonates
(weeks 5–52 postnatal)
Infants
(1–12 years)
Children
(12–16 years)
Adolescents 5

6. Fig. 10-1. Comparison of plasma drug levels in adults and infants.
A, Plasma drug levels following IV injection. Dosage was adjusted for body weight. Note that
plasma levels remain above the minimum effective concentration (MEC) much longer in the
infant. B, Plasma drug levels following subQ injection. Dosage was adjusted for body weight.
Note that both the maximum drug level and the duration of action are greater in the infant. 6

7. Drug Therapy in Neonates and Infants
Increased sensitivity in infants due to:
Immature state of five pharmacokinetic processes:
Absorption
Protein binding of drugs
Blood-brain barrier
Hepatic metabolism
Renal drug excretion 7

8. Pharmacokinetics: Neonates and Infants
Absorption
Oral administration (delayed gastric emptying, higher pH in stomach
Intramuscular administration (slow and erratic first few days of life)
Percutaneous absorption (increased toxicity because of thin skin)
Distribution
Protein binding- amount of albumin is low and other substrates compete for binding
Blood-brain barrier- immature, CNS drugs reach higher concentrations 8

9. Pharmacokinetics: Neonates and Infants
Hepatic metabolism: low at birth, mature by one year
Renal excretion: low from birth to a year 9

10. Pharmacokinetics: Children Age 1 Year and Older
Most pharmacokinetic parameters similar to those in adults
Drug sensitivity more like that for adults than for children younger than 1 year 10

11. Pharmacokinetics: Children Age 1 Year and Older
One important difference
Metabolize drugs faster than adults
Markedly faster until age 2 years; then a gradual decline
Sharp decline at puberty
May need to increase dosage or decrease interval between doses 11

12. Adverse Drug Reactions
Vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development
Age-related effects
Growth suppression (caused by glucocorticoids)
Discoloration of developing teeth (tetracyclines)
Kernicterus (sulfonamides) 12

13. Dosage Determination
Dosing is most commonly based on body surface area (BSA).
Initial pediatric dosing is, at best, an approximation (even when BSA is used).
Subsequent doses need to be adjusted.
See formula on next slide. 13

14. Dosage Determination Approximate dosage for a child =
Body surface area of the child × adult dose
1.73 m² 14