Lecture 6; Absorption and half life Flashcards
What is drug absorption?
Process of drug transfer from the site of administration to the systemic circulation
i.e Oral drugs need to be absorbed across the gut wall (biological membrane) and avoid first pass metabolism in the liver before they reach the systemic circulation. IV is direct. vs topically applied.
Describe and compare the oral vs IV PK?
IV, peak concentration is achieved immediately and then first order elimination can occur
Oral drugs take time to reach max concentration before elimination can occur(and not all makes it), but can absorb over a longer period of time
When it comes to absorption what is meant by Rate and Extent?
Rate: How rapidly does the drug get from the site of administration to the systemic circulation
Extent: How much of the administered dose enters the systemic circulation
- Bioavailability (F)
Describe how the combination of rate and extent can influence achieving therapeutic conc.
A drug can have a slow rate of absorption and not reach sufficient minimum therapeutic level
A drug can have a fast rate of absorption but a low extent and not reach minimum therapeutic level or only have a therapetuic level for a short period of time
What determines the extent of absorption (F)?
Fraction absorbed (f)
- Into portal vein from gut
- Physicochemistry
- Metabolism/efflux
i.e Being able to cross the wall somehow and that which is metabolised before it can
Describe the physiochemistry properties related to extent of absorption:
- Small, non ionised, lipophilic
- Soluble in gut (must be soluble to cross gut)
i. e theophylline (f=100)
i. e Gentamicin (large +ionized) f <5%
Describe how metabolism/efflux influences extent of absorption:
Metabolism/efflux
- Enzymes present in gut wall
- > (simvastatin metabolised by CYP3A4 f = 50%)
- Drug transporters
- > Digoxin effluxed by P-glycoprotein (f=65%)
Once medicines cross the gut wall, what determines the extent of absorption?
First pass metabolism in the liver (portal vein)
Hepatic extraction ratio (ER)
- Fraction of drug entering the liver that is extracted
- Dependent on organ clearance and blood flow
i. e Morphine ER = 60%
i. e Ethanol ER = 10-70% (depends on hepatic blood flow)
Describe and explain the equation for extent (F)
F = f . (1-ER)
The overall extent of absorption is called bioavailability. This is the fraction of the administered dose that reaches the systemic circulation. It can be absorbed across the gut (f) multiple by (1-ER)
What are the input processes?
Bolus - IV injection Zero order - constant IV infusion First order - i.e intramuscular injection or oral
Write some notes on zero order input
Zero order
- IV infusion
- Stomach emptying based drugs under physiological control
- Slow release formulation (pharmaceutical control)
i.e These methods are all constant rates of input. The peak concentration ends once the input stops
What is first order absorption dependent on?
First order
- Intestinal absorption
- > Diffusion limited
- > Dependent on concentration
- > Explained by Ka
- > 90% complete after 4x absorption T1/2
What is Ka when it comes to first order absorption?
Ka is the proportionality constant that relates the amount of a drug at the site of absorption to the rate of absorption.
Describe the time concentration relationship of a first order input:
Rate of absorption rapidly declines from onset, and peak concentration is achieved when Elimination rate = rate absorption
What are the applications when it comes to rate:
IV/Oral dose conversion -> Divide IV dose by F to get equivalent oral dose Time to peak concentration/effect -> i.e paracetamol concentrations Substitution of generic medicines - Rate (Cmax, Tmax) - Extent (area under curve)
