adme processes

Question 1

what patient characteristics influence drug absorption?

Answer 1

gastric emptying rate, intestinal motility, drug-food interactions

Question 2

what formulation characteristics influence absorption?

Answer 2

dosage form: tablet, capsule, liquids, coating

Question 3

drug characterisitcs affecting absorption:

Answer 3

solubility
lipophilicity
ionisation
chemical stability
liability for metabolism

Question 4

what is rate of absorption?

Answer 4

how quickly the drug reaches cmax

Question 5

what is extent of absorbtion?

Answer 5

the total amount of drug absorbed

Question 6

what caharacteristics are required for a drug to diffuse through a membrane?

Answer 6

small, unionised, lipohilic

Question 7

what is solubility

Answer 7

the extent to whic ha drug can dissociate in an aqueous solvent

Question 8

why is poor solubility bad?

Answer 8

can decrease absorption, reduce absorption rate, precipitate. needs a complex vehicle to allow ingestion, can cause inacurate in vitro results

Question 9

DMSO

Answer 9

organic solvent that can dissolve polar and non-polar compounds

Question 10

what is kinetic solubility

Answer 10

concentration before precipitation occurs

Question 11

how is kinetic solubility measured?

Answer 11

filter centrifugation followed by uv abs or hplc

Question 12

what is thermodynamic solubility?

Answer 12

complicated solubility that requires ph and temperature maintenance

Question 13

what are the pros and cons to kinetic and thermodynamic solubility?

Answer 13

kinetic soluility is high throughput and requires small compound amounts, but may not give true solubility.
Thermodynamic solubility is low throughput but gives true solubility

Question 14

how does ionisation affect absorbtion

Answer 14

ionised compounds are highly hydrophillic, therefore unable to be absorbed

Question 15

when are drugs ionised

Answer 15

acids are ionised in basic conditions, bases are ionised in acidic conditions. acids are more readily absorbed in the stomach, bases are more readily absorbed in the intestine

Question 16

why is lipophilicity important?

Answer 16

lipophilicity influences membrane passage, binding strength to metabolising enzymes, plasma proteins, herg ion channels

Question 17

what is permeability

Answer 17

the ability of a drug to diffuse across a cell membrane

Question 18

what assays are commonly used to determine permeability

Answer 18

caco-2 permeability

Question 19

what are caco-2 cells?

Answer 19

cancer cells that grow as a monolayer

Question 20

what is plasma stability

Answer 20

the drug stability in plasma environment

Question 21

why is plasma stability important?

Answer 21

drugs must pass through plasma to reach their site of action

Question 22

what are ABC transporters?

Answer 22

antigen binding cassette transporters

Question 23

what kind of transport do ABC transporters typically perform?

Answer 23

efflux transport

Question 24

what are SLC transporters?

Answer 24

solute carrier transporters

Question 25

what do SLC transporters do?

Answer 25

usually uptake transporters. passive transport through either facilitated diffusion, or transport against a conc. gradient by coupling transport to another substrate

Question 26

what kind of transporter is p-glycoprotein?

Answer 26

abc drug transporter

Question 27

what is its effect in the intestine?

Answer 27

it effluxes xenobiotics, limiting absorption

Question 28

what is its effect in tumor cells?

Answer 28

confers immunity to cytotoxic drugs

Question 29

what inhibits p-glycoprotein?

Answer 29

verapamil and technically substrate competition

Question 30

what induce p-glycoprotein?

Answer 30

rifampicin