Pharmacokinetic-pharmacodynamic model simulations

Gieschke R, Reigner BG, Steimer JL. Exploring clinical study design by computer simulation based on pharmacokinetic/pharmacodynamic modelling. Int J Clin Pharmacol Ther 1997 35 469-74. 

Duffal SB, Kimko HC (eds). Simulation for designing clinical trials a pharmacokinetic-pharmacodynamic modeling perspective (Drugs and the pharmaceutical sciences, Vol 127). New York Marcel Dekker, 2003... 

Simulation for Designing Clinical Trials A Pharmacokinetic-Pharmacodynamic Modeling Perspective, edited by Hui C. Kimko and Stephen B. Duffull... 

Gobburu, J. V., Marroum, P. J., Utilisation of pharmacokinetic-pharmacodynamic modelling and simulation in regulatory dedsion-... 

Pharmacokinetics and Pharmacodynamics, Modelling, Simulation, and Data Analysis 335... 

Bonate, P. L. Pharmacokinetic-Pharmacodynamic Modeling and Simulation. Springer, 2006. 

PURPOSE AND RATIONALE Pharmacokinetic/pharmacodynamic modeling and subsequent simulations may be applied to answer key questions during the drug development process. This example shows that a PK/PD approach could be used to determine whether reduction in exposure of a given drug by 25 % due to an interacting variable results in any clinically relevant effect. 

Within the past decade there has been significant interest in determining whether the use of clinical modeling and simulation software would increase the probability of conducting successful clinical trials (43). This approach incorporates the technique of pharmacokinetic-pharmacodynamic modeling that was discussed in Chapter 19 with the disease progression models described in Chapter 20. Although this type of a clinical development tool has considerable potential, the outcomes to date have been mixed. For example, this approach has identified the placebo-response rate for various disease states as an... 

Pharmacokinetic/Pharmacodynamic Modeling and Simulations in Drug Development... 

Pharmacokinetic/pharmacodynamic modeling plays an important role during the NDA submission and review phase by integrating information from the pre-clinical and development phases. Existence of a well-defined PK/PD model furthermore enables the reviewer to perform PK/PD simulations for various scenarios. This ability helps the reviewer gain a deeper understanding of the compound and provides a quantitative basis for dose selection. Thus, PK/PD modeling can facilitate the NDA review process and help resolve regulatory issues. ... 

Pharmacogenomics and Genomic Technologies / 2794 Pharmacokinetic/Pharmacodynamic Modeling and Simulations in Drug Development / 2802 Pharmacokinetics Effects of Food and Fasting / 2816... 

Bonate, P.L. Assessment of QTc interval prolongation in a Phase I study using Monte Carlo simulation. In Simulation for designing clinical trials A pharmacokinetic-pharmacodynamic modeling perspective. (Kimko, H.C. and Duffull, S., Eds.). New York, 2003... 

---