Pharmacology and Pediatrics

Age Groups of Pediatrics Population

Group Age

Preterm or premature Less than 36 weeks gestational age

Neonate Less than 30 days of age

Infant 1 month until 1 year of age

Child 1 year until 12 years of age

Adolescent 12 years of age until 18 years of age

Oral Drug Absorption in the Neonate vs Older Children and Adults

Drug Oral Absorption

Acetaminophen Decreased

Ampicillin Increased

Diazepam Normal

Digoxin Normal

Penicillin G Increased

Phenobarbital Decreased

Phenytoin Decreased

Sulfonamides Normal

AGE-RELATED PHARMACOKINETIC DIFFERENCES IN CHILDREN COMPARED WITH ADULTS

Premature Neonate Neonate Infant Child Adolescent

Absorption

Gastric acidity Decreased Decreased Decreased Equal Equal

Gastric emptying time Decreased Decreased Equal Equal Equal

GI motility Decreased Decreased Decreased Equal Equal

Pancreatic enzyme activity

Significantly decreased

Decreased Decreased Equal Equal

GI surface area Increased Increased Increased Increased Equal

Skin permeability Significantly increased

Increased Equal Equal Equal

Distribution

Body composition Equal

Blood-brain barrier Decreased Decreased Equal Equal Equal

Plasma proteins Significantly decreased

Decreased Equal Equal Equal

Metabolism

Liver Decreased Decreased Decreased Equal/Increased Equal

Elimination

Renal blood flow Decreased Decreased Decreased Equal Equal

Glomerular filtration Decreased Decreased Decreased Equal Equal

Tubular function Decreased Decreased Decreased Equal Equal

Drug Distribution

• Drug distribution in the neonate depends on– Amount of body water, body fat and drug binding

• Body water (BW)– Neonates have more BW than adults (70% vs 50%)– Full-term: 70% body weight is water– Pre-term: 85% body weight is water

• Body fat– Pre-term infants have much less fat than full-term– Lipid soluble drugs may not be accumulated

• Drug binding to plasma proteins– Binding of drugs to albumin is reduced– Drug competition for binding albumin may occur

Drug Excretion• GFR is much lower in newborns than in older infants,

children or adults

• This limitation persists during the first days of life and improves thereafter

• Neonatal GFR based on body surface area – Birth: Only 30-40% of the adult value– 3 weeks: 50-60% of the adult value– 6-12 months: Reaches adult values – Thus, renal elimination occurs is very slow initially

• Toddlers– Have shorter drug elimination (t½) than older children and

adults probably due to ↑ renal elimination and metabolism

Pediatric Dosage Forms

• Elixir– Alcoholic solutions in which the drug molecules are

dissolved and evenly distributed– No shaking is required– Generally, all doses contain equivalent amounts

• Suspension– Contains undissolved drug particles that must be

distributed throughout the vehicle by shaking– Caution: Risk of administering unequivalent doses may

lead to toxicity or lack of efficacy

• Prescriber awareness and care giver education on these differences is important

Compliance

• Compliance may be difficult to achieve since it involves many factors– Parent’s ability to follow directions– Measuring errors– Spilling and spitting out

• Recommendations to improve compliance– Pill boxes– Calibrated medicine spoon– Ask if parent gives another dose after spitting out– Stress importance of duration of treatment– Instruct whether to wake the child during q6h dosing– Give some responsibility to the child for his/her care

Pediatric Drug Dosage

• Most drugs approved for use in children have pediatric doses, stated in mg/kg

• If recommendations are not available, an approximation can be made by any of several methods

• Methods include : Age, weight, or surface area– Age: Young’s rule– Weight: Clark’s rule– Doses based on age or weight are conservative– Doses based on surface area are more adequate

• The calculated pediatric dose should never exceed the adult dose!

Clark’s Rule

• Formula for Clark's Rule is:

Weight of the child in pounds/150 ("normal" adult weight) X the usual adult dose

• The adult dose of a medication is 30 mg. The child's weight is 30 lbs. What is the correct dose?

30/150 = 1/5

1/5 x 30 mg = 6 mg • Preferred method

Young’s Rule

• Pediatric doses for children over the age of 2 based on the adult dose. Not as precise as Clark’s rule.

Take the age of the child in years and divide that by their age plus 12.

• Multiply this number times the adult dose.

Pediatric dose = [age/(age + 12)] x adult dose

• 2/14 X 250mg = 35 mg for a child age 2 yrs