Key Principles of Pharmacology

Based on data gathered during pharmacokinetic studies, Pharmacokinetics (PK), applying scientific and mathematical models helps to predict and understand the time course of Absorption, Distribution, Metabolism, and Excretion of medicines in the body.. This allows scientists to assess the relationship between the medicine’s beneficial and toxic effects, and to predict the safety and tolerability of the medicine in humans. Data gathered during pharmacokinetic studies are thus essential for determining dosing schedules in clinical trials. A favourable PK profile is vital to the therapeutic success of a medicine.  

Figure. 4: Concentration of medicine within blood plasma (Y axis) vs. time (X axis)   

If we give a person a medicine at time zero, we will see the concentration of the medicine go up and then fall slowly as it is eliminated from the body. In the first phase the medicine enters the body faster than it is being removed (absorption phase), and its concentration in the body increases to reach a maximum (Cmax.) at a certain time (Tmax.). Then, after the peak concentration has been reached, the medicine is eliminated from the body faster than it is entering, so the concentration of the medicine in the body starts decreasing (elimination phase).  

By plotting plasma concentrations of the medicine versus time, we can calculate the area under the curve (AUC (from time zero to infinity), expressed in units of μg x h/mL (μg × h/mL). Cmin in the graph may refer to the detection limit of the medicine, that is the minimum concentration measurable. Whenever the determination of AUC is partial (incomplete), the time period over which it is determined should be specified, for example, AUC0–12 h refers to area under the curve from time zero to 12h after administration. 

One further important parameter is the elimination half-life of a medicine, defined as the time it takes for the concentration of the medicine in the plasma or the total amount in the body to be reduced by 50% (T1/2 in the graph). In other words, after one half-life, the concentration of the medicine in the body will be half of the starting dose. With each additional half-life, proportionally less of the medicine is eliminated. However, the time required to reach half of the original concentration remains constant. In general, the medicine is considered to have a negligible therapeutic effect after 4 half-lives, that is, when only 6.25% of the original dose remains in the body. The elimination half-life is a useful pharmacokinetic parameter as it provides an accurate indication of the length of time that the effect of the medicine persists in an individual. It can also show if accumulation of the medicine is likely to occur with a multiple dosing regimen. This is helpful when it comes to deciding the appropriate dose amount and frequency. Along with other pharmacokinetic data and values about the individual patient, the half-life can help health practitioners to estimate the rate at which a drug will be eliminated from the body, and how much will remain after a given time period.