# 04 - Timing of sampling

# Timing of sampling

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The Maudsley® Prescribing Guidelines in Psychiatry
CHAPTER 11
to know when a drug is or is not at steady state but there are two concepts connected 
to steady state that are often misunderstood.
■
■Time to reach steady state follows a logarithmic pattern
The time taken to reach steady state is dependent on the drug half-­life – the time 
taken for concentration to fall by 50%. This table shows the rise to steady state.
Number of half-­lives
% of steady state reached
75%
87.5%
94%
97%
Most people know the adage that it takes four to five half-­lives to reach steady state. 
In fact, three half-­lives are sufficient for an approximation of steady state 
concentrations.
■
■Steady state is not always related to therapeutic activity
Blood levels at steady state are determined by dose and drug half-­life. The concentration at which therapeutic activity occurs is fixed (see later) and, during therapeutic 
dosing, is often exceeded before steady state is reached. Loading doses are sometimes 
used to achieve therapeutic concentrations as quickly as possible. Loading doses do 
not hasten the achievement of steady state levels.
Timing of sampling
Sampling time is vitally important for many but not all drugs. If the recommended 
sampling time is, say, 12 hours post-­dose, then the sample should be taken 11–13 hours 
post-­dose if possible; 10–14 hours post-­dose, if absolutely necessary. A study of clozapine samples taken 1 and 2 hours before and after the 12-­hour scheduled sample time 
showed a mean variation of clozapine blood concentration of less than 10%, but some 
individuals’ levels varied by over 50%.1 So, if a sample is not taken within 1–2 hours of 
the required time, it has the potential to mislead rather than inform. Always try to take 
samples as close to the scheduled time as possible. Obviously, if toxicity is suspected, 
take a sample straightaway, ignoring any scheduled timings.
For trough or ‘pre-­dose’ samples, take the blood sample immediately before the next 
dose is due. Do not, under any circumstances, withhold the next dose for more than 
1 or possibly 2 hours until the sample is taken. Withholding for longer than this will 
inevitably give a misleading result (it will give a lower result than that ever seen in the 
usual, regular dosing), and this may lead to an inappropriate dose increase. Sampling 
time is less critical with drugs with a long half-­life (e.g. olanzapine, aripiprazole) but, as 
an absolute minimum, prescribers should always record the time of sampling and time 
of last dose. This cannot be emphasised enough, and is worth repeating in bold. Always 
record the time of sampling and the time of the last dose.