Ideal sampling time for drug assays.

Estimation of the mean steady state serum concentration of a drug from an isolated sample apparently requires a knowledge of both the timing of the sample within the dose interval and of the pharmacokinetic constants of the drug in the individual. Data from 80 general medical outpatients receiving maintenance digoxin has been used to derive a relationship between the serum digoxin concentration at any given time (C) and the mean steady state concentration (C), but this did not allow for individual variation in drug handling. It can be demonstrated theoretically that, for a one compartment model with instantaneous drug distribution and first order elimination, the ratio, C/C, is dependent on the half time of the drug, the dose interval and the time of sampling. Moreover, for higher values of half time the ratio is virtually constant at 11 h after a daily dose. This, then, would be an ideal sampling time. The above approach can be extended to any drug provided that its half time is at least 15 h in healthy subjects and that the concentration/time curve approximates to a simple exponential decay during virtually the entire dose interval. Orally administered digoxin meets both of these provisions, the ratio at 11 h being 0.97, which is only slightly different from the 1.02 of the theoretical model. Ideal sampling times and the conditions under which they apply may be derived for other dose intervals.