The original college viva text reads:
This viva will test knowledge of pharmacokinetics and statistics. Draw the concentration time curve for an intravenous bolus of fentanyl. At this Viva candidates were asked to draw a concentration – time curve for an intravenous bolus of fentanyl, to label it and describe the information relating to that curve. Candidates were also asked about volume of distribution, half-life and clearance. In the second part to this Viva candidates were shown and asked to
describe various types of data, mean and median values, normal distribution and critical evaluation of a study.
To make this gibberish useable, it has been rewritten using the venerable Brandis physiology viva textbook as a template of style and depth.
Define a compartment as related to pharmacokinetics.
A pharmacokinetic compartment is a mathematical concept which describes a space in the body which a drug appears to occupy. It does not need to correspond to any specific anatomical space or physiological volume.
What is a single compartment model of pharmacokinetics?
A single compartment model of pharmacokinetics describes a drug being distributed in a single volume inside the body, from which it is then cleared.
- The compartment is characterised by a distribution volume, V
- Drug concentration is determined by the dose (I) and distribution volume
- Clearance is determined by the compartment elimination rate (k)
This can be represented as a diagram:
What assumptions are made when using this model?
- The drug is instantly and completely dispersed to every part of the compartment
- The drug is thereafter homogeneously distributed throughout the volume.
- The drug is not distributed to anywhere other than this compartment, i.e. it is not absorbed into the tissues.
For which drugs might this model be sufficient?
Drugs which are highly water soluble and which are confined to body water as a single compartment, for example aminoglycosides.
- High water solubility
- High molecular weight (confined to blood)
- Low protein/tissue binding
- No tissue metabolism
- Chemically stable (no spontaneous degradation)
Which properties of a drug might make it unsuitable for a single compartment model?
Give some examples.
- Highly lipophilic, eg. anaesthetics
- Highly tissue bound, eg. amiodarone
- Unpredictable elimination, eg. exhaled, metabolised by tissues, chemically unstable (spontaneous degradation)
What is a multi-compartment model?
A multi-compartment model accounts for the differences in the rate and volume of drug distribution to different tissues and body fluids. Each compartment represents a space which has distinct pharmacokinetic distribution characteristics.
Distribution of drugs from the blood into the tissues is an important factor in pharmacokinetics of anaesthetic drugs
What are the phases of distribution? Can you draw a diagram illustrating the three phases of distribution?
The three phases of distribution are
- Initial rapid distribution
- Second rapid elimination phase
- Terminal "slow elimination" phase
These phases can be expressed as a polyexponential curve of drug concentration over time:
The polyexponential curve has multiple exponents which can be interpreted as half-lives of each distribution phase.