Absorption and Half-life Flashcards
What are the two types of drug absorption?
The extent (2 things) and the rate of absoprtion
What is the fraction absorbed (f) governed by? (2 things)
The amount of drugs that goes into the portal vein via the gut.
Physiochemistry: theophylline is small and unionized, 100% vs gentamicin which is large and ionized, so less than 5%
Metabolism/transport: simavastatin is metabolised by CYP3A4 so 50% absorbed, and PGP transporter rids of digoxin, only 65% absorbed
What is first past extraction? (ER)
The drug removed while passing through liver.
Is related to blood flow, e.g morphine is 60% and ethanol is 10% -70%
What is the equation for extent of drug absorbed? The bioavailability
F= f. (1-ER)
e.g is 0.4 for morphine
What are the three different input processes that determine the rate of drug absoprtion?
Bolus: IV injection
Zero-order: constant rate IV infusion
First order: intramuscular injection
What can be said about zero order?
If a tablet is taken orally, the rate of drug delivery to the small intestine is the rate of gastric emptying and this is physiologically controlled. (The Tmax)
However drug manufacturers can alter how quickly the drug dissolves or is absorbed, due to slow release formulation. (Tk0)
The Tk0 is the duration of the process.
What can be said about first order?
The absorption across the intestinal wall.
It is diffusion limited as well as relies on the absorption half life of the drug (which is determined by the KA, a rate constant)
What are some applications of extent and rate of drug absorption?
Drug bioavailability, to convert IV dosage to oral doses. (extent)
Time of peak concentration and thus peak of effect. (rate)
Also the substitution of generic medicnies with same rate (Cmax and Tmax) and extents as generics.
What three processes can half life explain?
What is the half life equation?
Absorption, elimination and accumulation(the % of steady state)
ln2(0.7) x Volume of distribution/ clearance
How does half life influence elimination and accumulation? (graph and values to take from it)
After one half life, 50% of the drug has been eliminated and 50% has been accumulated (towards steady state)
After two half lives, 75% of drug accumulation has occurred and 25% of the drug is left due to elimination.
After four half lives, 93.8% of the drug has accumulated (of steady state), and the body concentration has reached 6.25% (94% elimination)
On a graph on concentration versus time how can you work out the half life?
Look for steady state (plateau) and divide by four (due to half lfe table discussed prior, after four half lifes we are at 94% of steady state.
If a drug with half life 8 hours is given every 8 hours, after about four times the half life, the concentration at steady state will be twice as high as it was after the first dose. (graph pg 76)
What is the accumulation factor show?
The conc at steady state over the conc after the first dose
What are some applications of half life?
Accumulation/Elimination:
Time to steady state (about four times the half life)
Time to eliminate drug (4 x the elimination half life)
Absorption: Time to reach peak concentration, Tmax is about 3 x the absorption half life. This happens before all the drug is absorbed because peak conc is when rate in = elimination
