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Design and Analysis of In-Vitro Pharmacokinetic Experiments

Tuesday 7th July 2015 - 14:30 to 15:00
INI Seminar Room 1
In many pharmacokinetic experiments, the main goal is to identify enzymes that are related to the metabolic process of a substrate of interest. Since most of the enzymes that are involved in drug metabolism are located in the liver, human liver microsomes (HLMs) are used in these in vitro experiments. Experimental runs are conducted for each HLM at different levels of substrate concentration and the response, the initial rate of reaction, is measured from each experimental run. The relationship between such a response and the substrate concentration is usually nonlinear and so it is assessed from the size of the nonlinear regression parameters. However, the use of different HLMs requires additional random effects and there might also be covariate information on these HLMs. A further complication is uncertainty about the error structure of the resulting nonlinear mixed model. Methods for obtaining optimal designs for such models will be described. The resulting designs will be compared with the larger designs used in current practice. It will be shown that considerable savings in experimental time and effort are possible. Practical issues around the design and analysis will be discussed, along with suggestions of how the methods are best implemented.
Presentation Material: 
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons