Lecture 18

Question 1

What are the major Pharmacokinetic covariates in children?

Answer 1

Size
Age
Organ function
Body composition
Drug interactions
Pharmacogenetics
Environmental factors
Circadian rhythms

Question 2

What are the size models which were attempted to allow the determination of appropriate doses in children/neonates?

Answer 2

Per Kg model
Body surface area model
Allometric model

Question 3

How effective is the per Kg model at predicting appropriate doses?

Answer 3

It under predicts the dose under 47 kg

The error increases as size decreases

Question 4

How effective is the body surface area model at predicting doses?

Answer 4

It typically over estimates the dose

Question 5

What are the key pharmacokinetic factors that need to be used when trying to translate dosages into children?

Answer 5

There is reduced clearance due to the fact that the liver isn’t fully developed so the heaptic enzymes are immature as well as due to reduced renal function

Question 6

What are the different ages that can be considered when determing a dose for a drug?

Answer 6

The post natal age however this not very useful as it does not account for in-utero maturation
Post menstral age which is on average 2 weeks longer than the biological age
The post conception age which is the biologicl age and the most useful age but it is not widely recorded

Question 7

How is drug absorption altered in neonates?

Answer 7

They have thinner skin resulting in more rapid neonatal drug absorption
There is an increased intragastric pH increasing the bioavailability of basic compounds like penicillin G
Decreased bioavailability for weak acids
There is delayed gastric emptying causing a delay in Tmax
There is reduced transport of bile salts
This results in decreased enetero-heptic circulation opiods