Pharmacokinetics Flashcards
(42 cards)
What is oral bioavailability (F)?
The fraction of the orally administered drug that reaches the systemic circulation
Factors affecting oral bioavailability of a drug?
-Poor absorption from the gut
-Breakdown of drug in gut
-First pass effect
What is the first pass effect?
- all drugs absorbed into intestine MUST first pass through liver via portal circulation
- drugs may be broken down in liver
- and so not all of drug may reach systemic circulation
What is the pKa of a drug?
the pH of a solution when 50% of the drug is ionized
What are the factors affecting drug absorption?
- Lipid solubility, as need to cross membrane
- pKa of drug: pH at which 50% is ionised
- pH at absorbing surface
What is meant by the term drug distrubution?
- penetration of drug into tissues and organs from the blood
- can be considered in terms of body compartments
- higher lipid solubility = higher ability to cross membranes therefore higher distribution
- if drug binds to (eg) albumin easily it too will have a higher distribution
- if high blood flow to that area, drug will have high distribution there
Apparent volume of distribution (Vd)
the volume of fluid which would be required to contain the amount of the drug in the body if it was equal to the concentration in the plasma
Vd =?
amount of drug in body/plasma drug concentration
What does a small Vd indicate?
that the drug is confined to body water, likely polar, and not well distributed
(conc is high in plasma)
What does a high Vd indicate?
- a high concentration of drug in extravascular space (concentrated in tissues, not in the plasma)
- most of the drug is contained in extraplasmic space & is unavailable for metabolism/elimination
What is drug elimination?
removal of the drug from the body
What 2 parameters control elimination?
Excretion and metabolism
How are drugs removed?
urine, faeces, milk, bile, vomit or if they are broken down
What does a drug with a short half life mean?
It is being eliminated by the body quickly
needs to be adminstered more often
What is clearance?
volume of plasma cleared of a substance per unit time
What are the features of first order kinetics?
- Most common
- t0.5 is constant
- clearance not changing
- higher clearance when higher Cp
What are the features of zero order kinetics?
- Less common, rate of process is independent of drug concentration.
- Happens when elimination process is saturated
- Half life does change, eg if you give a smaller dose of the drug your half life will be smaller
What is the First order elimination equation?
T0.5 = ( 0.693 * Vd) / clearance
What is the main difference between the IV bolus curves and the oral admin curve?
- Peak of oral curve shows when absorption and elimination are equal
- No absorption phase in IV bolus as no Cp doesn’t go up
What is intravenous infusion?
- here the drug is eliminated as it is perfused
- plasma conc goes up until Css is reached
Rate of infusion =?
Css x Clearance
Css
Steady state concentration
Rate of infusion = rate of elimination
How many half lives does it take to reach steady state?
around 5
What does a oral dosing graph look like?
- Peaks and trough of oral dosing with every dose
- But when these peaks and troughs are steady/ dont really change value, this is when the Css average is reached
