A simple approach to estimate the variability of individual plasma drug concentrations in patients at a standardized multiple dosing regimen.

Equations were derived to simulate the course of plasma drug concentration versus time curves for a multiple dosing regimen of drugs with a long biological half-life in those cases when Vrel and t1/2 or k in a particular subject do not correspond to the average values underlying the calculation of a standard dose. Extreme course can be expected only when Vrel and t1/2 show deviation from the average values in the opposite direction. Thus, smaller Vrel and longer t1/2 result in an increase, greater Vrel and shorter t1/2 in a decrease in plasma drug concentration after giving the standard dose. An analysis of the course of plasma drug concentration curves at the loading phase permits the estimation of the actual t1/2 in the particular subject. As an application example, the loading phase of digitoxin is presented. The procedure allows an individual dosage adjustment on the condition that plasma drug concentration in the particular subject can be monitored regularly.