L29 - recap of bioavailability, dissolution, membrane transport

what the drug does to the body

what the body does to the drug

amount of drug that reaches its site of action and the rate at which it gets there

• Liberation • Absorption • Distribution • Metabolism • Excretion

• release: drug dissolves at administration site • absorption: drug crosses biomembrane to reach blood

• this is typical of hydrophilic molecules • you can increase bioavailability by changing drug structure, e.g increase lipophilicity)

• typical of lipophilic molecule • optimisation of dosage form

• salvation of drug at crystal surface to create stagnant layer of saturated solution • diffusion of dissolved molecules across layer into bulk solution - observed rate of dissolution depends on slowest of these 2 steps

dissolution rate = dC/ dt = D x S /h (Cs-Cb)

• solubility (Cs) of weakly acidic drug predicted by: • pH of sol • pKa • solubility of ionised drug (S0)

• solubility of weakly basic drugs can be predicted given: • pH of sol • pKa • solubility of unionised drug (S0)

• major pathway • passive diffusion: solutes diffuse down a conc gradient. partiton into lipid bilayer and then out to cytoplasm • aqueous pore: hydrophilic channel made by aquaporin proteins • facilitated diffusion: selective, carried protein, down conc gradient • active transport: selective, against conc gradient

system not in equilibrium moves towards equilibrium, so flux/flow must occur

J = C x v x A conc x velocity x area

change in conc

• flux increases with membrane surface area • SA of the SI is bigger than stomach • flux is inversely proportional to membrane thickness (Δx). • flux is correlated to difference between drug conc on either side of memb

• k quantifies distribution of drug between membrane and aqueous phases which it separates • K = Coil/Cw • K= ratio of drug’s solubility in 2 phases • K= drugs relative affinity for oil compared to water

octanal water partiton coefficient - used to find drugs lipophilicity

absorption, distribution, elimination

deposited in fatty tissue

to bind to receptors + ensue,es by h bonds

• measures drug lipophilicity • P = [drug]oct / [drug]water

P= 10 LogP = 1

P= 100 LogP= 2