02.05.2 Elimination Half-Life

The elimination half-life is the time from the maximum concentration to half maximum concentration. The elimination half-life is dependent on the rates of metabolism and elimination of the drug. Thus, slowly metabolised and slowly eliminated drugs will have long half-lives. Whereas, rapidly metabolised and rapidly eliminated drugs will have short half-lives. The half-life is an important determinant of the frequency a drug needs to be administered. Drugs with short half-lives need to be given more often than those with long half-lives.

Provided there is a method for measuring the levels of the drug in the plasma, we can graphically plot the drug concentration against time (Figure 2.10).

Figure 2.10 Elimination half-life (Copyright QUT, Sheila Doggrell)

In Figure 2.10, Drug A was administered intravenously, giving a maximum concentration straight away, and then the concentration diminishes over time, as the drug is metabolised and excreted. The elimination half-life is the time from the maximum concentration to half maximum concentration. Thus, we need to determine the 50% maximal response, and then determine the time from maximal to half-maximal response, which with Drug A is about 4.4 hours. Drug A will have to be administered at least 2 times a day, and maybe more, as it is rapidly metabolised and/or eliminated.

Elimination half-lives can also be determined when drugs are administered orally. When Drug B is administered orally, it has to be absorbed into the blood stream, so blood levels rise slowly over time to a maximum. Once again, the elimination half-life is the time from the maximum concentration to half maximum concentration. So we need to estimate the time of the maximal response, which is about 6.2 hours for Drug B. The levels of Drug B have fallen to half-maximal after 13.4 hours. Thus, the elimination half-life is 13.4 – 6.2 hours, which is 7.2 hours. Drug B may be suitable for administration 2 times a day or less, as it is less quickly metabolised and/or eliminated than Drug A.