Detailed monitoring recommendations and information regarding peak and trough sampling
For drugs with a long half-life compared to the dosing interval, because little drug is eliminated during a dosing interval, the time the sample is collected is not important since concentrations do not change much during the dosing interval. Bromide, phenobarbital and zonisamide are examples, although phenobarbital and zonisamide half-life may get short enough that timing is important. For this reason, for anticonvulsants, we always recommend a trough (just before the next dose) sample so you can assess the lowest concentrations that occur during a dosing interval.
For drugs with a short half-life compared to the dosing interval, much or almost all drug will be eliminated during the dosing interval. As such, no single sample can predict drug concentrations at any other time in the dosing interval. The question then is peak versus trough or both? Both is indicated if a half-life is to be calculated or if it is important to know how high and low concentrations occur. If only a single sample can be collected, the choice depends on the drug. For anticonvulsants with a short half-life, because we are interested in the lowest concentration that occurs during a dosing interval and a trough is recommended. For cyclosporine, in humans, a peak concentration has been associated with the best prediction of overall exposure to drug during a 12 hour dosing interval and ideally, if only a single sample can be collected, it would be peak. However, in veterinary medicine, the timing of drug concentrations collected as part of scientific clinical research reports generally was not given, so guidance is problematic. If a 24 hr dosing interval is used for cyclosporine, the half-life may be so short that drug is no longer detectable at 24 hrs. As such, if both a peak and trough cannot be collected, a peak is preferred. Consistency is important: the same time should be used if comparison across time is desired. If the patient has not responded well, at that time, both a peak and trough should be considered. For antibiotics, in general both a peak and trough (or second sample 2 to 3 half-lives later) is important to design a dosing regimen.
Calculating a half-life: Determining the patient’s half-life for a drug might be important and for such drugs, both a peak and trough sample should be collected, with the trough always being before the next dose. The exception of a trough sample is if the half-life is so short that no drug is likely to be present (e.g. aminoglycoside antimicrobials), then the second sample should be collected two to three half-lives after the first sample. A half-life can be calculated based on the slope of the line resulting from the two points: half-life (hr) = 0.693/kel where kel = (ln[peak/trough])/time elapsed between peak and trough (ln=natural log).