Age and Drug Dosing

Question 1

How does absorption vary with age?

Answer 1

Absorption is low when young, tends to reach adult levels when 5.
Older adults: more variable, but increased in high ER drugs

Question 2

In what age group(s) are albumin levels decreased?

Answer 2

Neonates
Infants
Older adults

Question 3

In what age group(s) are alpha1-acid glycoprotein (AAG) levels decreased?

Answer 3

Neonates

Not altered if a healthy adult

Question 4

How does volume of distribution change with age?

Answer 4

Childen: reduced (normal at 5)
Older adults: depends on the drug.
- If distributes into lean body tissue the Vd will decrease.
- If distributed into fat Vd will increase.

Question 5

How does the kidney and renal function change with age?

Answer 5

• Mass decreases after 40
• Renal blood flow is low in neonates/infants/older adults. Normal at 1.
• Glomerular and tubular function follow the same pattern.

Question 6

How does the liver and hepatic function change with age?

Answer 6

• Mass is a high % of body weight in neonates/infants/children
• In older adults, mass drops with increasing age
• Liver blood flow is reduced in neonates/infants/children. Normal at 1-2.
• Liver blood flow decreases with increasing age

Question 7

How do CYP levels change with age?

Answer 7

• Low in neonates/infants. Normal at 1.
• In kids generally high and drops at puberty
  BUT there is no difference in 2C19 and 2D6
  The time of peak and rate of decline is different for each.

Question 8

How does UGT glucuroidation vary with age?

Answer 8

Low in neonates/infants. Normal by 2-3.

Question 9

How is dosing effected by PK parameters in infants?

Answer 9

Decreased absorption, metabolism, renal elimination.

Need higher doses.

Question 10

How is doing effected by PK parameters in children?

Answer 10

Decreased absorption from high gastric pH, immature GI transporters.
Need nigher doses.

Question 11

How is dosing effected by PK parameters in older adults?

Answer 11

More variable.

May have increased absorption due to low first pass metabolism if high ER drugs.

Question 12

How does hypoalbuminemia effect the free fraction and total concentration of phenytoin?

Answer 12

In adults and neonates albumin is low.
–> high fraction is unbound/free
Can lead to toxic levels in the plasma!

Question 13

What is the effect on total drug and unbound concentrations of phenytoin in young and older adults?

Answer 13

The total plasma concentration is the same.
Older adults have low hepatic metabolism and low protein binding.
–> Leads to a higher free fraction in older adults

Question 14

What factors determine how well drugs pass into breast milk?

Answer 14

1) Fraction unbound
<20% won’t cause plasma concentration >10% in baby
Note: only an unbound drug can pass into milk. And many drugs with Fu >20% don’t produce clinically relevant concentrations in baby
2) Transporters (BCRP)
3) Lipid solubility

Question 15

Why is RID for useful than milk/plasma ratio?

Answer 15

RID indicates the actual level of exposure for the infant.

Milk/plasma ratio is misleading. You could have a high ratio with no or low levels in the infant.