adme processes Flashcards
learn specifics of ADME
what patient characteristics influence drug absorption?
gastric emptying rate, intestinal motility, drug-food interactions
what formulation characteristics influence absorption?
dosage form: tablet, capsule, liquids, coating
drug characterisitcs affecting absorption:
solubility lipophilicity ionisation chemical stability liability for metabolism
what is rate of absorption?
how quickly the drug reaches cmax
what is extent of absorbtion?
the total amount of drug absorbed
what caharacteristics are required for a drug to diffuse through a membrane?
small, unionised, lipohilic
what is solubility
the extent to whic ha drug can dissociate in an aqueous solvent
why is poor solubility bad?
can decrease absorption, reduce absorption rate, precipitate. needs a complex vehicle to allow ingestion, can cause inacurate in vitro results
DMSO
organic solvent that can dissolve polar and non-polar compounds
what is kinetic solubility
concentration before precipitation occurs
how is kinetic solubility measured?
filter centrifugation followed by uv abs or hplc
what is thermodynamic solubility?
complicated solubility that requires ph and temperature maintenance
what are the pros and cons to kinetic and thermodynamic solubility?
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
how does ionisation affect absorbtion
ionised compounds are highly hydrophillic, therefore unable to be absorbed
when are drugs ionised
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
why is lipophilicity important?
lipophilicity influences membrane passage, binding strength to metabolising enzymes, plasma proteins, herg ion channels
what is permeability
the ability of a drug to diffuse across a cell membrane
what assays are commonly used to determine permeability
caco-2 permeability
what are caco-2 cells?
cancer cells that grow as a monolayer
what is plasma stability
the drug stability in plasma environment
why is plasma stability important?
drugs must pass through plasma to reach their site of action
what are ABC transporters?
antigen binding cassette transporters
what kind of transport do ABC transporters typically perform?
efflux transport
what are SLC transporters?
solute carrier transporters
what do SLC transporters do?
usually uptake transporters. passive transport through either facilitated diffusion, or transport against a conc. gradient by coupling transport to another substrate
what kind of transporter is p-glycoprotein?
abc drug transporter
what is its effect in the intestine?
it effluxes xenobiotics, limiting absorption
what is its effect in tumor cells?
confers immunity to cytotoxic drugs
what inhibits p-glycoprotein?
verapamil and technically substrate competition
what induce p-glycoprotein?
rifampicin
