Topic 7: Preclinical PK studies Flashcards
1
Q
Data needed to predict the likely PK profile
A
- LogP
- Caco-2 cell line permeability
- microsomal stability assay
- plasma protein binding drug transport
PK profile from this data is predicted using a series of scaling factors of the PBPK approach which assumes the body is made up of a series of compartments connected by blood flow that corresponds to organ systems
2
Q
Design of a pre-clinical trial
A
- CT curve needs 10-15 data points
- high in frequency soon after dosing, concentrated around CMAX
- 3 points in the absorption phase
- Samples should be ranged in a way to provide the most information from each mouse
- Data used to determine cMax, Cl and AUC
3
Q
Principles of allometry
A
- anatomical and physiological parameters between species can be correlated as a power function of body weight
- found by plotting body mass vs metabolic rate on a log scale and taking the slope
- Cl human = Clmouse*(weight human/weight mouse)^0.75