12.0 Bioavailability: physicochemical factors

bioavaliability

the propoertion of a drug or other substances that enters the bloodstresm when introduced into the body and is avaliable for theraputic action

for drugs administered orally

bioavaliability considers the fraction that survives first pass metabolism through the liver and is absorbed into th e systemic circulation

bioavaliability is critical

for determining a drugs effectiveness

boiavaliability is other words 

is the fraction of an administered emdication that reached circulation in its unchanged form

intravenous IV administration

100% bioavaliability, F=1,

because the drug is directly introduced into theblood stream bypassing the digestive system/ liver

therefore the entire dose is immediately avaliable for use by the body

orla administration

passes through the GI tract and is subject to first pass metabolism in the liver

these processes often reduce the amount of srug that enters the systemic circulation

orally administered drugs typically have less that 100% bioavailability 

calculating bioavaliability

• AUC. area under curve: total drug exposure over time, 

  • devived from a grapg that plots plasma drug concentration Vs time

  • AUC reflects hom much of the drug enters the bloodstresm and remains there over a given period

• D_oral and D_IV: represent the dose of the drug administered orally/ intravenously respectively

  • the formula takes accounts for dose differences so comparisions are mad eon equivelent basis

blue line represent sth eplasma conc of a drug following oral admin

the curve shows how the drug is absorbed over time, reaches peak conc then is gradually eliminated form the body

green line represents th eplasma conc after IV admin

the drug enters the blood stream immediately resulting in a sharp rise in plasma conc

shaded area under curve represents rhe AUC:

• AUC_IV is larger, showing that the entire dose administered intravenously enters the blood stream

• AUC_oral is smaller, showing that only a portion of th eoral dose reaches systemic ccirculation due to absorption barriers and metabolism

the differenc ebetween AUCs of oral and IV routs 

reflects how much the drug reaches the blood stram and contributes to the drugs thereputic effect

several physiochemical proeprties of a drug as well as physiological factroers within the body influence its bioavaliability

top hat drug absorption + diff formulations reread