Do we know that substances in blood are being transported around our body by vehicles known as ‘plasma proteins’?
In a field known as pharmacokinetics, scientists study how the differential binding of drug to plasma proteins and tissue proteins defines how extensively the drug is being distributed to the bodily organs.
The more extensive a drug is distributed, the higher its apparent volume of distribution (V), the longer it stays in the body (half life), and the less frequently it should be administered!
A question arises.
Given V = Vp + VT*(fu/fuT) (Gibaldi & McNamara Equation), will increase in free drug fraction in plasma (fu) increase or decrease V of a given drug?
Answer: It depends.
- In principle, an increase in fu increases V proportionally. This is conceptually logical for drugs with large V (>1 L/kg), as more free drug enters the tissues.
- However, this is not true for drugs with a small V (<0.2 L/kg). Why? Despite the increase in fu, these drugs are ‘intrinsically’ poorly distributed and V is minimally affected.
Take home message: The change in plasma drug binding impacts V of drugs of large V but not those of low V. Dose regimen adjustment may be applicable to the former but not the latter.
Read also: Biological Molecules Notes for Bachelor Students
Resource Person: Eric Chan, PhD