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Back to basics: pharmacokinetics

By Alison Thomson

As experts on medicines, pharmacists should be able to select the most appropriate drug for an individual, recommend the dosage regimen that is most likely to achieve the desired therapeutic response with minimum risk of toxic effects and monitor the effects of a drug, if appropriate. In order to do this, the principles of pharmacokinetics and pharmacodynamics need to be applied. Most pharmacists will remember learning these at university but not all will have kept them at their fingertips. It is important to appreciate that these principles are fundamental to the current practice of clinical pharmacy and may become even more significant as pharmacists expand their roles into prescribing.

Pharmacokinetic equations describe the relationships between the dosage regimen and the profile of drug concentration in the blood over time. Pharmacodynamic equations describe the relationships between the drug concentration-time profile and therapeutic and adverse effects. By controlling the plasma concentration-time profile of a drug, we can ensure that the patient receives optimum treatment.

Initiating treatment

When a patient requires treatment with a new drug, a loading dose can be given so that therapeutic concentrations are achieved quickly. Loading doses are commonly used in acute conditions, such as status asthmaticus or status epilepticus, or if the drug has a long elimination half-life (eg, digoxin).

Volume of distribution

In many respects, calculating a loading dose of a drug is similar to calculating the amount of drug required to achieve a desired concentration in a flask of liquid (ie, dose = volume x concentration). Conversely, the volume of the flask can be estimated if the amount of drug and the measured concentration are known (ie, volume = dose ÷ concentration).

In clinical practice, the volume of distribution of a drug (V) can be estimated from a known dose and measured concentrations. Because concentrations are typically analysed in blood, serum or plasma, the estimate represents the “apparent” volume throughout which the amount of drug would need to distribute in order to produce the measured concentration. For example, if two drugs, A and B, are both given as 100mg intravenous bolus doses and the measured plasma concentrations are 10mg/L and 1mg/L, the corresponding volumes of distribution would be 10L and 100L, respectively.

Variability in apparent volume of distribution between drugs reflects the proportion of the administered dose that remains in the plasma. Drugs that are watersoluble or highly bound to plasma proteins have a high plasma concentration relative to the dose, hence small volumes of distribution. In contrast, drugs that are lipid soluble or bind extensively to tissues are present in plasma in low concentrations and, therefore, have large volumes of distribution.

Download the attached PDF to read the full article.

Citation: The Pharmaceutical Journal URI: 10997062

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