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Statistical Analyses in Clinical PPK/PD Studies Bridging Studies using NONMEM Yoshiro TOMONO Clinical Pharmacology Biometrics, Biometrics, Pfizer Pharmaceuticals Inc., Tokyo Summary: The present paper reports a new approach to building a population pharmacokinetic and phar macodynamic model (PPK/PD) and interpreting clinical data. In design of PK studies for the bridging strategy, a simple formula which gives the 90 per cent confidence interval to prove no ethnic PK difference is proposed, which derives the approximate estimation method for calculation of power and sample size for the parallel group design. In clinical studies, it is important to apply a technique to analyze the linking model with the drug concentra tion (pharmacokinetics, PK) and the efficacy (pharmacodynamics, PD) which are related closely. Effect compartment model and Jusko-type indirect PD model examples are shown using PPK/PD model analyzed with NONMEM. Recently the validation method of NONMEM is concerned. The bootstrap approach has been to use to ass ess the stability and predictive performance of a pharmacokinetic model developed using NONMEM. Guidance for Industry: Population Pharmacokinetics suggested the use of the bootstrap procedure as a satisfactory method for the validation and checking of population models in the drug approval process. Although validation methods are still being evaluated and may require further testing. The PPK/PD approaches are hopeful about the future in the field of drug development and drug evalua tion. Key words: Population pharmacokinetics, Pharmacodynamics, NONMEM, Effect compartment, In direct model, Bridging study, Interoccasion variability, Model varidation, Bootstrapping

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