Following multiple dosing over several days of treatment, the maximum and minimum concentrations of drug achieved after each dose reach constant levels. This is termed the �steady-state�. Steady-state pharmacokinetics are generally described using five parameters (Figure 1).
Figure 1. Drug concentration over time. Defining pharmacokinetic parameters.
Cmax: peak plasma concentration
- Cmax is the highest observed plasma concentration achieved during a dosing interval
Tmax: time to reach Cmax
- Tmax is the time taken to reach the highest observed plasma concentration
Cmin: minimum (trough) plasma concentration
- Cmin is the lowest observed plasma concentration achieved during a dosing interval. Cmin is also called the �trough concentration�
AUC: area under the curve
- AUC is the total plasma exposure achieved during a certain time period. After repeated dosing, it is often expressed as the plasma exposure over a 24-hour period (AUC0�24). AUC is derived from the area under the plasma concentration versus time curve (shaded area in Figure 1)
T1/2: half-life
- This is the time taken for the plasma levels of drug to fall by 50%. Drugs with a short half-life are eliminated rapidly from the body; those with a long half-life remain in the body for a longer period of time. If a PI has a long half-life, or if the half-life can be extended, there is the potential for less frequent dosing (e.g. twice- or even once-daily)
