435-bioavailability 1

bioavailability

fraction of the admin dose that reaches systemic circulation

absolute F

IV dosage form compared to oral

relative F

oral dosage form compared to oral dosage form (no IV)

F equation

(AUC iv/dose iv) / (AUC tab/dose tab)

AUC

reflects the total amount of drug exposure

larger AUC

large F

low F

due to poor intestinal absorption and/or high hepatic metabolism (first pass)

F=Fa x Fg x Fh

Fa-amt that survived absorption

Fg-amt that survived gut metabolism [usually insignificant]

Fh-amt that survived hepatic metabolism

well absorbed drug

already absorbed a lot so even when a prokinetic is given, AUC doesnt change much; only the Cmax and tmax is earlier/faster

poorly absorbed drug

when given a anticholinergic the AUC does change because now more of the drug can be absorbed which inc F

prokinetic

faster gastric emptying=quicker intestinal transit= not the best absorption if too fast but okay for a well-absorbed drug

anticholinergic

delays gastric emptying=longer intestinal transit time=greater F

enzyme inducers

encourage metabolism so more metabolism occurs=less F [reduced drug effect]

enzyme inhibitors

inhibit metabolism=greater F [toxicity caution!]

clearance

volume of drug-containing plasma that is cleared per unit of time [tells us how efficiently the body is clearing the drug]

CLb (blood clearance)

volume of blood containing drug that is cleared per unit of time

CLoral

clearance after an oral dose; includes absorption

Cl oral is inversely realted to F

as Cl oral inc, F dec

CLh (hepatic clearance)

clearance done by the liver via metabolism or biliary excretion

CLh = CL + CLr

if there is no CLr then CL=CLh

CLr (renal clearance)

clearance done by the kidneys via filtration, secretion, and reabsorption

CLr = CL-CLh

CLr = fe x CL

plama V is half of the blood V

drug is half less in blood than in the plasma

(ex-2mg/ml drug in blood means 1mg/ml drug in plasma)

no drug binding to RBC

Cb/Cp = 0.5

if a drug is mainly distributed in the plasma then

it will have smaller VD in the plasma

if a drug is mainly distributed in the RBS then..

it will have a smaller VD in the blood

if a drug is mainly distributed in the plasma then AUC plasma

is greater than AUC blood (by half)

fe

fraction of drug eliminated unchanged in the urine

hepatic metabolism & renal metabolism are the major excretion pathways so..

if fe=0.2 that means 20% was excreted unchanged in the urine and 80% was excreted hepatically

fe = CLr/CL

as fe inc, CL dec

F= CL/CL oral

F = AUC po/ dose po / AUC iv/ dose iv