General drug pharmacokinetics
In this step, we will provide a general introduction to pharmacokinetics (PK), explaining the terminology and its importance. Pharmacokinetics is the study of what the body does to a drug and how the drug is distributed and excreted. It can involve complex mathematical modelling, but for the purposes of this course, we will stick to outlining the most important parameters governing PK.
Antibiotics differ in their pharmacokinetic behaviour. It is vitally important these properties are appreciated in order to ensure the safe and effective use of these drugs in various clinical situations, such as renal failure, obesity, and sepsis.
The following are the major pharmacokinetic parameters:
| Pharmacokinetics Step | Definition |
|---|---|
| Absorption | The amount of drug that is absorbed is determined by the bioavailability. This is the percentage of an administered dose that reaches the systemic circulation. |
| Distribution | Distribution refers to the movement of a drug to and from the systemic circulation and various tissues (e.g fat, muscle and brain tissue) and the relative proportions of drug in the tissues. |
| Metabolism | Occurs by gastrointestinal bacteria or at the gastrointestinal mucosal level and by the liver prior to the drug reaching the systemic circulation. This will affect the amount of active drug available to have an effect. |
| Excretion | Excretion is the intrinsic ability of the body to remove a drug from the blood or plasma. The actual amount of drug removed will depend on both clearance and the plasma concentration of the drug. |
The image below shows the drug moving through the body and its effects.
Other important factors to consider are:
- Only the free, unbound drug is pharmacologically active, therefore the amount of protein-bound drug can influence its effect.
- Volume of distribution (Vd) is a size measurement of the compartment necessary to account for the total amount of drug in the body. It is determined by the plasma and tissue binding properties of the drug as well as its affinity for lipid versus water.
- Half-life (t1/2) is the time taken for the total concentration of a drug in the body to decrease by one half. This influences the time the drug’s concentration takes to reach a plateau in the blood, known as ‘steady state’. The half- life can also be used to determine how long it will take to eliminate all of the drug from the body.
The PK of a drug can be described as linear or non-linear.
- Linear PK is where changes in drug concentration depends only on the current concentration of that drug and the half-life will remain constant, irrespective of how high the concentration is. It essentially means that the concentration of the drug is proportional to the dose as PK parameters are unchanged.
- Non-linear PK is usually due to saturation occurring in one of the PK mechanisms such as protein binding or renal metabolism. Changes in drug dose do not equate to a proportionate change in the drug concentration as PK parameters are changed.
It can be useful to predict the maximum concentration (Cmax or peak) and minimum concentration (Cmin or trough) produced by a drug during the dosing interval at steady state. This is particularly important for any drug with a narrow therapeutic index / therapeutic range, which is the range of doses at which it is effective without unacceptable adverse events. For drugs with a narrow therapeutic index, it is critical to achieve an acceptable peak concentration for therapeutic effect whilst ensuring that the trough levels fall below a specified concentration to avoid toxicity.
In this step, we have covered the most important aspects of PK and how they can affect the concentration of a drug. Whilst this step has focused on PK, PD is also important to consider when prescribing drugs and this will be discussed more in the next step.
Optimise Aminoglycoside Use in Clinical Practice
Optimise Aminoglycoside Use in Clinical Practice
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