Bioavailability
Bioavailability = AUCoral / AUCiv;
The relative amount of drug that reaches the greater systemic circulation (i.e. following absorption & first-pass metabolism)
It is the proportion of drug that gets into the plasma compared to if you injected the same amount IV.
In order to get to the plasma the drug goes through:
Ingestion
Transit to GI tract
Absorption in small intestinal mucosa
First pass metabolism in small intestinal mucosa and liver
Bioavailability is used to determine:
The optimal route to achieve the therapeutic concentration.
The amount of drug that needs to be given orally.
Pharmacokinetics - Absorption
Oral absorption in the GI tract
Stomach: Little absorption takes place for most drugs here (thick gastric mucous layer prevents significant drug absorption).
Small intestine: Transit time 4-6h; 6-7 m long x 2.5cm internal diameter.
It has a larger surface area (30-35m^2) than the stomach (~1m^2), due to:
Jejunal plicae circulare (circular infoldings) - increases surface area 1.6x
Epithelial villi + microvilli: increases surface area 80-100x.
Additional factors aiding absorption:
Peristalsis churns the intestinal contents, ensuring regular contact between drugs & epithelium.
pH is 6-7 (weakly acidic) —> determines the ratio of drug molecules that exist in the ionised and unionised state.
Transiting the GI epithelium into the bloodstream
4 methods:
Method of transit
Substrate
Passive diffusion
<500Da, lipophilic, not ionic
Facilitated diffusion
<500Da, Lipophobic, ionic drugs
Active transport
Ionised drugs
Pinocytosis
Large molecules
Passive Diffusion
The commonest way for many drugs to cross lipid membranes (Esp. if small [<500 Da] & not strongly ionic).
Lipophilic drugs (e.g. steroids) easily pass through lipid bilayers.
A note on absorption + pH:
Facilitated Diffusion