ADME 3

Question 1

what must drugs be in in order to be absorbed?

Answer 1

in solution-i.e dissolved

Question 2

how do most drugs cross membranes?

Answer 2

passive diffusion

Question 3

what membranes are lipophilic?

Answer 3

–rate-limiting to onset
–stomach wall–
cell membranes–
blood-brain barrier

Question 4

what 2 compounds are actively transported?

Answer 4

a-amino acids

sugars

Question 5

how does a drug behave with two immiscible liquids?

Answer 5

Equilibrium is set up between the two phases depending on the relative affinity for each

Question 6

what is the equation for the partition coefficient (P)?

Answer 6

conc of drug organic/ conc of drug aqueous

Question 7

what does a high partition coefficient imply?

Answer 7

highly lipophilic drug

Question 8

low is P also written?

Answer 8

Log P , Log10P

Question 9

How do you measure the partition coefficient?

Answer 9

shake flask
HPLC
Calculated Log P (cLogP)

Question 10

if the Log P is less than 0, or P is less than 1 what does it imply?

Answer 10

favours the organic side

Question 11

what kind of modeling does the partition coefficient allow for?

Answer 11

quantitative modeling- how readily does a drug partition between the two media

Question 12

does the partition coefficient apply to ionised or unionised drugs?

Answer 12

unionised

Question 13

what is the shake flask method?

Answer 13

• Drug is allowed to equilibrate between two immiscible liquids
• Layers are separated and the concentrationin both layers is determined

Question 14

how do you partition ionisable drugs?

Answer 14

All ionised drug will reside in the aqueous layer
Unionised drug will equilibrate
between organic and aqueous layers

Question 15

what is P app?

Answer 15

Apparent partition coefficient at a particular pH•pH dependent –degree of ionisation will change with pH

Question 16

what is P true?

Answer 16

partition coefficient of the unionised form of the drug

Question 17

what is the rages of P app?

Answer 17

0-P true

Question 18

what are the ranges of Fu?

Answer 18

0-1

Question 19

what is the formula for Papp?

Answer 19

pAPP=p truex fu

Question 20

does the formula for papp apply to partially ionised bases?

Answer 20

yes

Question 21

what are weak acids most lipophilic in?

Answer 21

acidic environments

Question 22

what are weak bases most lipophilic in?

Answer 22

alkaline environments

Question 23

why is it difficult to measure p true expermentally?

Answer 23

as almost no drug would be left in aq environment

Question 24

for weak acids what does p app decrease with

Answer 24

increasing ph-Drug becomes more water soluble with increasing pH as it becomes more ionise