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Multiple Dose

With this refresher, drug pharmacokinetics after multiple dose administration may be easier to understand.

Aspirin given for a headache may be given as a single administration, whereas aspirin for arthritis will be given as a multiple dose. Antibiotics are usually given as a multiple dose regimen to produce and maintain effective plasma concentration. In fact, many drugs are given this way; anti-hypertensives, anti-epileptics etc.

Multiple dose administration is a very common method of drug administration. Up to this point we can calculate the drug concentration in plasma at any time after a single dose, we will continue now by looking at the equations for multiple dose administration.

Multiple IV Bolus

After a single dose administration we assume that there is no drug in the body before the drug is administration and that no more is going to be administered. However, in the case of multiple dose administration we are expected to give second and subsequent doses before the drug is completely eliminated. Thus ACCUMULATION of the drug should be considered. On repeated drug administration the plasma concentration will be repeated for each dose interval giving a PLATEAU or STEADY STATE with the plasma concentration fluctuating between a minimum and maximum value.

We have already looked at the shape of the plasma concentration versus time curve following a single intravenous administration. If we assume instantaneous mixing we start off with an initial concentration, Cp⁰, calculated as Dose/V and then we have a fall in concentration with time controlled by the elimination rate constant.

Independent Doses

Figure 25.3.1 Drug Concentration after Two Independent IV Bolus Doses

If the doses are given far enough apart then the concentration will have fallen to approximately zero before the next dose. There will then be no accumulation of drug in the body.

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