Pediatric PK/PD- Metabolism

Question 1

Phase I metabolism involves what enzymes?

Answer 1

CYP families

Question 2

3A4 in kids

Answer 2

Starts as 3A7, then goes to 3A4

3A4 matures to adult levels by 1 year of age

Question 3

2C19 in kids

Answer 3

Activity increases in the first 6 months of life

Question 4

2E1 in kids

Answer 4

Reaches ~80% of adult levels by 1 year old

Question 5

1A2 in kids

Answer 5

Absent in neonatal period, reaches 25% adult levels by 1 year old, 55% by the age of 9

Question 6

Phase II metabolism of APAP goes through what processes?

Answer 6

Glucuronidation and sulfation

Question 7

What happens in an APAP OD?

Answer 7

Glucuronidation pathway is saturated and APAP is oxidized to NAPQI

Question 8

Why are newborns and kids <12 protected from APAP toxicity?

Answer 8

More of the APAP metabolism goes through the sulfation pathway in this age group so there’s a lower risk of rapidly saturating the glucuronidation pathway

Question 9

In the first year of life, there is ____ drug metabolism of drugs that get metabolized by ____

Answer 9

There is decreased drug metabolism of drugs that get metabolized by 3A4

Question 10

2C19 metabolism in young infants-5 years of age

Answer 10

There are increased rates of metabolism by 2C19 in young infants and there are faster 1/2-lives, but normalizes around the age of 5.

Means that drugs that get metabolized through 2C19 (like PPIs) need to be dosed more often