Paediatric Pharmacokinetics

Question 1

What’s a Pre-term baby?

What’s a Full-term baby?

What’s a Neonate?

What’s an Infant?

What’s a Child?

What is Drug dose and response affected by? What does this stand for?

Answer 1

• <37 weeks
• 37-42 weeks
• Up to 4 weeks
• Up to 1yr
• 1-12yrs
• ADME - Absorption, Distribution, Metabolism, Excretion

Question 2

ABSORPTION:
Oral:
What are the properties of the gut that affect drug absorption in a Neonate?

Intravenous:
Why is this so commonly used?

What does it put one at risk of?

Why is it a difficult route at times?

Intramuscular:
What is absorption based on?
→ What are these like in Premature babies?

Percutaneous:
Why are Topical corticosteroids avoided with Neonates?

Rectal:
When is this route used?

Answer 2

• • High Gastric PH at birth due to Underdeveloped gastric mucosa (= ↓Acid secretion)
  • ↑Acid-labile drug absorption e.g. Penicillin
  • ↓Peristalsis and Bile production
  • GIT disorders affect absorption

• 100% Bioavailability
• Infection
• Difficulties in line access (needle insertion) and drug compatibilities

• Muscle’s Mass, Perfusion, and Contractions
• Mass and Perfusion are Low, and Contractions are inefficient

• Can cause significant systemic effects as they have a large surface area : body weight ratio

• If Oral/IV is unavailable, They refuse oral medication, Vomiting

Question 3

DISTRIBUTION:
It’s affected by:
1. Body composition - What’s it like in Neonates?
→ How does this affect the drug doses given? Why?

2. Plasma protein binding - What’s it like in Neonates?
   → What conditions affect protein binding? How?
   → How can this be dangerous?
3. BBB development - What’s it like in Neonates?
   → What affects its permeability?

Answer 3

1. Higher total body water and Lower body fat
   → Requires larger initial doses to achieve the target serum concentration as the drug can distribute into the extracellular water
2. Reduced plasma protein conc. and binding affinity
   → Malnutrition, Nephrotic syndrome, Sepsis, Hepatic disease, which all cause LOW ALBUMIN
   → There’s competition for binding sites by endogenous compounds, which can displace protein-bound drugs = ↑Free drug = Toxicity
3. Functionally incomplete
   → Acidosis, Hypoxia, and Hypothermia

Question 4

METABOLISM:
Where does it take place? What’s this like in Neonates?

Phase I - What is it? What occurs here?
→ What’s it like in Neonates?

Phase I - What is it? What occurs here?
→ What’s it like in Neonates?

Answer 4

• Liver - Underdeveloped and matures rapidly after birth
• Hydroxylation - Makes drug more lipid-soluble to enhance renal excretion
  → Deficient in neonates and worse in premature babies due to immaturity of required enzymes
• Sulphation, Methylation, and Glucuronidation - Makes drug more water-soluble
  → Glucuronidation very immature in neonates

Question 5

EXCRETION:
What is Renal function in children affected by?

What has to be monitored to check renal function?

Answer 5

• Sepsis, Dehydration, and Nephrotoxic drugs

- Serum Creatinine, eGFR, and Urine output

Question 6

ADVERSE DRUG REACTIONS:

In Neonates, why can there easily be an adverse drug reaction?

Answer 6

Immature liver function prevents detoxification and excretion = Accumulation of drug in blood