Drug Disposition in Paediatric

MEDICATION USE IN
PAEDIATRIC

IZZATI ABDUL HALIM ZAKI
[email protected]

Drug disposition Absorption

● Pharmacokinetic factors Excretion Distribution

○ Essential to Metabolism
understand the
variability in drug
disposition among
children.

○ Rational and
appropriate therapy.

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Drug disposition: Absorption

● Oral

○ Influenced by few factors;
■ Gastric & intestinal transit time, gastric & intestinal pH and gastrointestinal contents.

○ Rate of absorption correlated with age
■ Older infants & children = healthy adults

● Intramuscular

○ Infants & children > neonates
○ Increased muscle blood flow
○ VERY PAINFUL & SHOULD BE AVOIDED IF POSSIBLE

● Rectal

○ Useful during vomiting
○ Infants & children reluctant/unable to take oral medication.

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Drug disposition: Absorption

● Topical

○ Absorption greatly related to skin hydration.
○ Newborn > infants > adults

● Intranasal

○ Medications with local action.
○ Intravenous access is difficult.

● Inhalation

○ Direct delivery of medication to the lung.
○ Mainstay treatment for asthma.

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Drug disposition: Distribution

● Factors determine drug distribution changes with age.
● Total body water and extracellular fluid decrease with age.

Age Total body water (%) Extracellular fluid (%)

Neonate 75 45

3 months 75 30

1 year 60 25

Adult 60 20

● Water - soluble drugs required larger doses in neonates compared to older 10
child to achieve similar plasma concentrations.

Drug disposition: Distribution

● Binding to plasma protein in infants is low.

○ Low concentrations of globulin and albumin.

● Binding capabilities compared to adults
reached within;

○ Third year of life - acidic drugs
○ 7 to 12 years of life - basic drugs

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Drug disposition: Metabolism

● At birth

○ Reduced amount of enzymes responsible for drug metabolism.
○ Various immature body systems.
○ Reduced capacity for metabolic degradation.

● Older infant & young children (1 to 9 years age group)

○ Increase metabolic rate.
○ Greater metabolic clearance compared to adult.
○ Required higher dosage to achieve similar plasma concentration.

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Drug disposition: Excretion

● At birth

○ Kidney is anatomical and functional immature.
○ Limit the renal excretory capacity.

● Below 3 to 6 months of age

○ Glomerular filtration rate lower than adult.

● 6 to 8 months of age

○ Complete maturation of glomerular and tubular function

● After 8 months of age

○ Renal excretion comparable with older children and adults.

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Drug disposition: Other factors

● Nutritional status

○ Malnutrition - low albumin level affecting protein binding
capacity

● Disease states

○ Cystic fibrosis - high excretion of antibiotics
○ Nephrotic syndrome - increased excretion of furosemide
○ Cardiac failure - altered protein binding

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