Pharmacokinetic/Pharmacodynamic Models and Methods

  • Davide Verotta
  • Lewis B. Sheiner


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).


Drug Concentration Spline Function Nicotine Concentration Linear Spline Semiparametric Approach 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Davide Verotta
    • 1
    • 2
  • Lewis B. Sheiner
    • 1
    • 3
  1. 1.Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Anesthesia, School of MedicineUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Laboratory Medicine, School of MedicineUniversity of CaliforniaSan FranciscoUSA

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