Unless therapeutic drug monitoring is being used to forecast a dose or there are concerns about toxicity, samples should be taken at steady state [4-5 half-lives after starting therapy
At steady state, plasma concentration is usually proportional to receptor concentration. Some drugs, such as perhexiline, which has a very long half-life in patients who are 'poor metabolisers', should be monitored before steady state is achieved to prevent toxicity developing after the first few doses. Another example where early monitoring may be useful is after phenytoin loading, where measurement of the plasma concentration can give a preliminary indication of adequate dosing.
The timing of the collection of the sample is important as the drug concentration changes during the dosing interval. The least variable point in the dosing interval is just before the next dose is due. This pre-dose or trough concentration is what is usually measured. For drugs with long half-lives such as phenobarbitone and amiodarone, samples can be collected at any point in the dosage interval.
Correct sample timing should also take into account absorption and distribution. For example, digoxin monitoring should not be performed within six hours of a dose, because it will still be undergoing distribution and so plasma concentrations will be erroneously high.
Occasionally, sampling at the time of specific symptoms may detect toxicity related to peak concentrations of, for example, carbamazepine and lithium.
For once-daily dosing of aminoglycosides, the timing of the blood sample is determined by the method of monitoring. For example, it is collected 6-14 hours post-dose when a nomogram is used, or twice within the dosing interval to calculate the area under the concentration-time curve. When aminoglycosides are prescribed in multiple daily doses to treat, for example, enterococcal endocarditis, then trough samples are measured to minimise toxicity and assess whether concentrations are adequate for efficacy.
TDDDaily MaintenanceAgePOIV/IMPOIV/IMPremature neonate201553–4Full term neonate30208–106–81 mo– 10 yr and