Lecture 3: Absorption and Half-life Flashcards
Extent (F) is what?
two components?
f - fraction absorbed into the portal vein from the gut
- due to the physicochemistry as well as metabolism/transport
ER- first past extraction
- drug removed while passing through the liver due to organ clearance and blood flow (morphine has a high ratio of removal whilst the enzymes for ethanol are easily saturated)
- blood flow determines this based off how much time it spends in the liver, high blood flow means it moves in and out fast.
F = f x (1-ER)
Input processes?
- bolus (instantaneous)
- zero-order (constant IV for defined period)
- first-order (intra-muscular proportional to amount in muscle - similar to oral absorption)
Rate (Zero-order)
The stomach is bad at absorbing, the small intestine is good.
The rate of absorption is based off gastric emptying = physiological control
NB: some drugs are formulated to be released slowly = Pharmaceutical control
Zero order input, where does the peak conc occur?
At the end of the constant rate input
Rate (first order) ?
when does peak conc occur?
Intestinal absorption
- the proportionality constant relating drug amount at the site of absorption to the rate of absorption is often called KA
- This is first order and is exactly related to the half life for the absorption process
PEAK CONC. OCCURS WHEN THE ABSORPTION RATE EQUALS THE ELIMINATION RATE (after this more is going out than in, before this there is still more to go)
Half-life equation?
absorption half life equation?
T1/2 = (0.7 x V) / CL
absorption Hlife = 0.7/KA
What is the accumulation factor?
depends on what?
the ratio of the concentration at the steady state to the concentration after the first dose at the same time after the dose.
- dosing interval
- Half-life
half lives till steady state?
half lives till peak conc reached?
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