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概要

A Useful Microsoft Excel Add-in Program for Modeling Steady-state Enzyme Kinetics

Baojian Wu, Roland Ako and Ming Hu

In vitro metabolism and inhibition studies, which serve as the basis of predicting pharmacokinetic events in vivo , are an essential part of pharmaceutical development and research. With the increasing occurrences of a typical kinetic profiles, modeling of enzyme kinetics is no longer a one-step operation of fitting classical Michaelis-Menten equation to the data. It involves considerable computational works regarding model selection and discrimination. This study presented XL Kinetics, a free Microsoft Excel add-in program written in Visual Basic for Application (VBA), for enzyme kinetic analysis. The program provides 11 most frequently used enzyme (stead-state) kinetic models including the models describing atypical kinetics (i.e., substrate inhibition, sigmoidal and biphasic models), a bisubstrate compulsory ordered model, and four reversible inhibition models. To evaluate the program, modeling results from XL_Kinetics and the commercial software packages (i.e., GraphPad Prism and Sigma Plot) were systematically compared. The results show that the kinetic parameters and their respective standard errors derived using XL_Kinetics are essentially the same as those obtained with the commercial software’s. In conclusion, XL_ Kinetics automates enzyme kinetic analysis in MS Excel, and may provide drug researchers and students with a fast, reliable and easy-to-use tool for routine analysis of enzyme kinetic data.