Introduction to PK - Half-life
Hi everyone.
In the last video, I promised to cover Distribution, but I think I should show you a bit about what the Half-life is all about before we go to the Distribution and Clearance videos.
We have talked about the ADME of Pharmacokinetics in the previous videos. ADME is represented by what we call the 4 Primary and independent pharmacokinetic parameters – Rate of Absorption, Bioavailability, Volume of Distribution and Clearance.
Half-life is actually not one of the Primary parameters. It is a derived parameter – and dependent on Volume of Distribution divided by Clearance.
Half-life is defined as the time taken for concentrations to fall by half, or 50%. Here in this graph the half-life is 12 hours, and you can see that at the end of the first 12 hours, the concentrations have fallen by 50%. After that, following each 12 hours, the concentrations fall by 25%, 12.5%, 6.25% and 3.125%, respectively so that by the end of 5 half-lives, concentrations are only about 3.125% of the original concentration. So approximately 97% of the administered dose is lost by the end of 5 half-lives.
We conveniently round it up, to say, complete drug elimination requires 5 half-lives.
In a multidose regiment, the accumulation occurs in a mirror image fashion to elimination, and we conveniently say that Steady State drug concentrations are achieved after 5 half-lives. This is a mathematical reality, and is independent of how long the half-lives, dose and dosing intervals are.
Steady State concentrations are achieved at 5 half-lives. Period.
Note however, that for this drug that has a half-life of 12 hours, being dosed at 12 hourly dose interval, the fluctuations between maximum and Minimum is about 2 fold. Similarly, the concentrations at steady state compared to the first dose is also about 2 fold. This is accumulation. We will look at these effects again in a later video, so just keep this in mind for the time being.
Observe how as the dosing interval shortens to 6 hours, the time to reach steady state remains unchanged. However, the fluctuations reduce and the accumulation increase. Conversely, when you increase the dosing interval to 24 hours, while the time to reach steady state remains unchanged, the fluctuations increase and the accumulation decreases. The steady state concentrations all this while remains exactly the same.
That’s all for now. I hope this has helped you have an understanding of what half-life is all about. In the next video we will look at the process of Distribution. Until then. Bye.