Volume of distribution Flashcards
Define Volume of distribution
It is the apparent volume into which a drug disperses in order to produce an observed plasma concentration
Vd = Dose / Plasma concentration
Units: L or L/kg
What are the major determinants of volume of distribution
Drug properties which affect protein and tissue binding
- Molecular size
- Charge
- pKa
- Lipid/Water partition coefficient
What are the patient factors that determine the Vd
- Age
- Gender
- Body muscle / fat proportion
- Level of hydration
- Water distribution (oedema / effusions / ascites / pregnancy)
- Extracorporeal sites of distribution (circuits / filters / oxygenator)
What limits the equation Vd = Dose / [Plasma Drug]
It is limited by the multicompartment model of drug distribution.
I.e. when do you measure the plasma concentration after the dose is administered?
the drug concentration will vary over time depending on the time the drug takes to distribute around the body.
How is V(initial) calculated and what is it used for
Extrapolate a line of best fit (along the initial distribution phase) until time zero. the point of intersection of the imagined time zero line of this line is the V intitial.
It is used to calculate the Vd of the central compartment.
- -> this is determined by the degree of protein binding
- -> Highly protein bound drugs will have larger V-initial
What is V initial specifically used for
For therapeutic purposes, it can be used to estimate high peak plasma concentrations so that - if needs be - you can divide your loading dose to avoid toxicity
How is V (extrapolated) calculated and what is its use
Ignore initial peak (early concentration measurements)
Extrapolate a line to the slow stages (flatter gradient) of the terminal elimination phase of the concentration time curve – late concentration measurements
This is extrapolated back to the time 0 line and this concentration is used.
No defined clinically use
