5 - Extent and rate of absorption Flashcards
Extent of absorption - things that affect this, equation
F - extent of overall absorption into blood stream
F = f . (1-ER)
F - extent of absorption
f- Fraction absorbed by gut
- depends on physicochemistry of molecule (small unionized - easily cross e.g theophyilline)
- P glycoprotien (digoxin) , metabolism enzymes (CYP3a4
ER - first pass extraction ratio (fraction of drug entering liver that has been extracted)
- high metabolizing enzyme capacity (intrisnsic clearnace)
- blood flow (if slow - gives more time for liver to clear things)
Bolus, Zero-order, First order Input processes
Bolus - large amount of IV at once (absorption is instantaneous)
Zero-order - constant rate IV, or emptying of stomach to gut (input processes is constant for some amount of time)
First order - Intramuscular injection - drug goes where site of action is (absorption rate is proportional to amount of drug at absorption site)- absorption rate is higher immediately after the dose is given, rate then decreases as drug is absorbed
-gut wall absorption
First order, what is KA , absorption half life
First order - Intramuscular injection - drug goes where site of action is (absorption rate is proportional to amount of drug at absorption site)- absorption rate is higher immediately after the dose is given, rate then decreases as drug is absorbed
-gut wall absorption
- Proportionality constant relating drug amount at the site of absorption to the rate of absorption is often called KA
- related to half life of absorption process
- time of peak conc occurs when rate of absorption is equal to rate of elimination (normally after 3 half lives)
Absorption half life - 0.7/Ka (amount of time it takes for half of the drug to be absorbed)
IV/oral dose conversion
IV/F = oral dose
Time of peak concentration
the rate of drug absorption is a key determinant of the time of peal conc and thus of the peak effect
Peak effect - is the effect at the time Tmax of the peak conc (Cmax) - peak effect not same as the maxiumum possible effect of drug (Emax)
3 x absorption half life
-when absorption rate is equal to elimination rate
Generic medications
Important for controlling drug costs for healthcare. Generic drugs are much cheaper than original
-Regulatory authorities can use the rate and extent of absorpiton to judge if a generic drug is bioequialent to the original product
-rate is usually judge on basis of equivalent Cmax and Tmax while extent is jduged on Area under curve
Zero - order
Constant rate - e.g stomach emptying , IV constant
Tmax - time at where Cmax occurs - and this is controlled by stomach emptying (this is rate limiting step of absorption because in duodenum drug is absorbed very quickly)
-some drugs designed not to dissolve as quickly - means that the drug physiology could be the rate limiting factor for absorption
Half life (fractions absorbed)
= 0.7/KA - absorption or 0.7V/CL - eliminaion half life
describes a first order process
-Elimination half life - determins how quikcly a drug accumulates (accumulatin half life)
Half life number and conc 0 - 100% elimi - 0 1 - 50% elim - 50 2 - 25% elim - 75 3 - 12.5 elim - 87.5
Accumulation in constant, vs 8 hr vs 16hr
Accumulation - time course of drug is given constant or every 8 or 16 hours and in the end all have the same accumulation as teh constant rate
Accumulation Factor
Ratio of conc at steady state to conc after the first dose (at same time after the dose)
All drugs accumulate, the extent of accumulation depends on the dosing interval and half life - formal predicting accumulation is shown above. if doseing interval is equal to the half life then theaccumulation facotr is 2.
Tmax
is when conc is at peal - and this is when drug absorpiton equals drug elminitaiton - occurs before drug absorption is complete
tmax aprox 3 x absorption half life
