Gustafson

Question 1

What is PK? PD?

Answer 1

PK: dose -> exposure
PD: exposure -> response

Question 2

Is dose proportional to exposure?

Answer 2

Generally yes. There is a variability

Question 3

PK parameters for IV bolus of infrequent doses?

Answer 3

• Cmax: toxicity, efficacy
• AUC: exposure
• Terminal Half-life:

Question 4

PK parameters for multiple doses given frequently?

Answer 4

Cmax, Cmin, t1/2, Tmax

Question 5

What should you measure in the blood for prodrugs like cyclophosphamide PK studies?

Answer 5

The active metabolite (4-OH-CP)

Question 6

What is the difference between PK of CP and 4-OH-CP in dogs and cats?

Answer 6

Dogs are the best at metabolizing CP. Very effective CYP450. CP and 4-OH-CP tell a very different story. The drug itself seems like you are underdosing.
Cats don’t metabolize CP a lot, so CP and 4-OH-CP look quite the same.

Question 7

Is DOX exposure variable?

Answer 7

A lot. The same dosage of 30 mg/m2 is used, but some dogs can show ~X2 exposure more than others. Nothing will predict that variability.
Intra-patient variability can be as high as inter-patient variability.

Question 8

Is VBL exposure variable?

Answer 8

Even worse. ~7X variability

Question 9

What is the endpoint of phase I clinical trial?

Answer 9

Toxicity
Only do safety and PK.