Variability due to environmental differences

Question 1

What is the most important quantitative determinant of drug dose

Answer 1

Body size/ weight

Question 2

What is the most important consideration in prescribing in relation to body size

Answer 2

Loading and maintenance dose and volume of distribution changes

Question 3

What is the allometric scaling factor and why

Answer 3

3/4. Because of the overheads of bones/ blood vessels etc.

Question 4

What is the relationship between size, volume of distribution and drug loading doses

Answer 4

Directly translatable

Question 5

What is the relationship between size and maintenance dose

Answer 5

Non-linear. Predictable based on allometric scaling factor of 3/4

Question 6

For most drug what is the best predictor of clearance in terms of body size

Answer 6

Fat free mass and fat does not hold cytochrome enzymes so no drug metabolism. Exception is some lipophillic drugs

Question 7

What are the fold difference in loading dose and maintenance dose in relation to body size

Answer 7

500 fold, 100 fold (latter due to allometric scaling)

Question 8

What is the fold difference in drug clearance in relation to differences in renal function

Answer 8

10 fold

GFR 7L/h in healthy young adult, 0.5 L/h in terminal renal failure. There is always some non-renal clearance

Question 9

Prediction of renal function

Answer 9

Creatinine clearance / normal clearance based on population values

Question 10

How can creatinine clearance be calculated

Answer 10

Serum creatinine

Question 11

How can hepatic clearance be estimated

Answer 11

Difficult to predict without administering the drug, liver function tests (AST/ASL) not a good predictor of actual liver function

Question 12

Maturation of drug clearance for full term infants and preterm infants

Answer 12

Typical maturation for is about 30% after scaling for size.

Premature infants are around 10%

Question 13

Relationship between age and drug clearance

Answer 13

Age has a minor influence around 25% lower once weight and other factors such as renal function have been calculated

Question 14

What age does a child reach adult values of GFR and clearance maturation of most drugs

Answer 14

2 years

Question 15

Why at two years old do children need a higher dose relative to their size than any other age

Answer 15

Because clearance is greatest at two years of age