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Summary of the PhRMA Survey of TDI Practices• On technical aspects of TDI:Common PracticesDivergent PracticesPooled human liver microsomes (100%)The same major P450 enzymes testedLC-MS/MS for measurement of probesubstrates (100%)Solvent control at each time point (- testarticle + NADPH) are used (100%)Determine the log-linear phase of enzymeinactivation (100%)Conduct control incubations withoutNADPHReplicate determinations of K I and k inactare conductedPositive controls are includedTest article depletion not measuredFold dilution used during IC 50 shiftdeterminations range from no dilution togreater than 10-foldNumber of NME concentrations used todetermine inactivation parameters (6 orgreater)Number of time-points used (4 to >6)Data AnalysisLog-linear regression (k obs )followed by non-linear fitting todetermine K I and k inact parametersReciprocal plot (e.g., Kitz-Wilson) toestimate K I and k inactGlobal non-linear regression32