JSM 2004 - Toronto

Abstract #301437

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Activity Number: 259
Type: Topic Contributed
Date/Time: Tuesday, August 10, 2004 : 2:00 PM to 3:50 PM
Sponsor: Biopharmaceutical Section
Abstract - #301437
Title: Multiple Drug Interactions--A Flexible Approach
Author(s): Matthew L. Fidler*+ and Steven E. Kern
Companies: University of Utah and University of Utah
Address: 421 Wakara Way, Suite 318, Salt Lake City, UT, 84108,
Keywords: response surface ; synergy ; antagonism ; additivity ; interaction ; modeling
Abstract:

Drug therapy strategies maximize the desired effect(s) and minimize the negative side effect(s) often employing combination therapies. To classify, predict, and summarize these interactions, modeling is used. Modeling classification is based on Loewe standards, which adherence to caused inflexibility in changes in maximum effect and Hill slope. Minto suggested a model that deviated from this allowing flexibility, butleaving behind the single-constants to indicate interaction type. We propose a model similar to Minto's that allows single-parameter interaction statements, compares real data fits to Minto's model, and compares the error between Loewe reduction and Minto's noninteracting reduction. The following conclusions are made:(1) the current model fits as well as Minto (compared by AIC), (2) the model allows approximate assessment of additivity as proposed by Loewe, and (3) the model allows flexibility in surfaces, and (4) the model allows parameter-based statements, letting statistical tests such as interaction type and asymmetry to be performed.

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