Pharmacokinetics Malarkey Flashcards
How can the change in concentration of plasma drug concentration?
C(t2) = C(t1) x e-Kt
What type of input is an IV bolus?
No input, K
- no absorption
- all enters body in one go
What type of input is an IV infusion, patch or depot injection?
Zero order, K0
- released over a period of time
What type of input is an oral, inhaled, transdermal, intramuscular or sub-cutaneous injection?
First order
- rate changes over time
- amount of drug decreases over time
What pharmacokinetic factors change if the same drug is administered?
Absorption changes
- DME stays the same
- distribution
- metabolism
- excretion
What is the concentration of the drug in the body proportional to?
Dose
- referenced to a particular time after dosing
- 5 mins
- 10 mins etc
- two distinct doses
- second twice as much as the first
- proportional increase in amount (concentration) of drug in the body at the corresponding time point
What is the rate of elimination of drug from the body proportional to?
Concentration of drug in the body
How can K be calculated from concentration of drug being removed from the body?
Ct = Dose/V x e-Kt
What is elimination half life?
Pharmacokinetic parameter that is defined as the time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%
What is half life an important factor in?
Rate of elimination Duration of action Interval between doses Time for steady state Time for complete elimination
What is the equation to calculate K from half life?
K = ln2 / t1/2
What is the equation to calculate Clearance or Volume of Distribution from K?
K = CL/V
What parameter will inform Css average levels?
Clearance
What parameter will inform how long it takes to achieve steady-state?
Half life
How do enzymes and transporters display first order and zero order kinetics?
First order = as substrate concentration increases the rate of reaction increases
Zero order = as enzyme/transporter becomes saturated, there is not further increase in rate of reaction
What is volume of distribution?
Pharmacokinetic parameter that may be defined as the “apparent” volume into which the drug distributes in the body once equilibrium has been achieved
What is an apparent volume?
Even after drug equilibrium through the body, the drug concentrations are not homogenous in the body’s tissues
- drug concentrations in plasma will not be the same as concentration in brain, liver, muscle, fat etc
How can volume of distribution be determined?
Plasma drug concentrations after intravenous drug administration
Why can’t volume of distribution be determined after oral dosing or an intramuscular injection?
Don’t know how much actually gets into the blood
Why are drug concentrations not homogenous through the body tissues?
Tissues vary in their characteristics and perfusion
- bone is different from fat
- blood flow per gram weight of tissue
A drug’s physiochemical properties will mean it can permeate to varying extents
- some tissues more
- some tissues less
Tissues possess different kinds of transporters through which drugs may gain access to intracellular sites which they would not other be able to do based on simple membrane diffusion
Plasma and tissue binding of drugs
What is Fu?
Fraction unbound
- total mass of drug in plasma that is unbound
How can Fu be calculated?
Fu = drug concentration in plasma (free) / drug concentration in plasma (total)
How long does it take to achieve equilibrium in different tissues?
The time to achieve equilibrium is the same for each tissue
What is equilbrium?
Point at which drug throughout all tissues behaves kinetically the same
