Pharmacokinetic/Pharmacodynamic Models and Methods
Non-steady-state drug concentrations and concomitant pharmacological effects are an attractive data source for learning about dose-response, because experiments can be done quickly, and hence in available clinical settings. However a potential pitfall of this kind of experiment is clear from a plot of effect and drug observations vs time: often the two resulting curves seem to be “out of phase”. To give an example, the upper panels of Figure 1 show simulated data with the maximal value of the effect occurring before the maximal drug concentration. The reverse situation is shown in the lower panels of Figure 1: the maximal value of the effect occurs after the maximal drug concentration. In either case a plot of observed effects (connected in time order) vs observed drug concentration describes a loop. A “literal” interpretation of such a plot suggests that different effect levels occur at the same drug concentration level (at different times).
KeywordsDrug Concentration Spline Function Nicotine Concentration Linear Spline Semiparametric Approach
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