L8 - Prodrugs

what is a prodrug

an inactive precursor of a drug, converted into its active form in the body by metabolic processes

what are prodrugs designed to do

maximuse the effectiveness of a drug

what problems could prodrugs tackle (5)

• solubility

• poor membrane permeability

• drug toxicity

• bad taste

• short duratioj of action

what is mandatory for successful oral administration

• no acid lability

• good lipophilic balance

• resistance to stomach and liver enzymes

what is acid lability

a drug is unstable in acid conditions and tends to break down

labile = unstable / easily altered

why are prodrugs useful for drugs given intravenously

as higher concentrations and lower volumes can be used

what are polar prodrugs used for

improving the absorption of non polar drugs from the gut

why must drugs have some water solubility if they are to be absorbed

they will dissolve in adipose tissye and fail to interact effectively with the gut wall

how do chemists improve properties like solubility

attaching an extra chemical group

explain how using a prodrug for chloramphenicol can make it easier to absorb

chloramphenicol as an antibiotic has poor water solubility, so we make it into chloramphenicol succinate (a prodrug) by attaching a succinate group (an extra -cooh)

adding this makes it more polar and water soluble

after injection, enzymes remove the succinate group and is left behind as a harmless byproduct

how can you make oestrone easier to absorb

oesterone is used in HRT, and has poor water solubility, adding lysine to oestrone forms L-lysyl-oesterone

lysine has extra polar groups which makes the drug much more water soluble
releases active oestrone and the lysine is a harmless byproduct

how do you seperate the ester from the prodrug to create the active version and the harmless by product

hydrolysis

attaching a hydrophobic group like an ester to polar drugs creates what?

a prodrug that is less polar and more lipophilic and can diffuse more rapidly