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A Model To Investigate Drug Interactions for Positive and Adverse Effects


E. Zanderigo, V. Sartori, G. Sveticic, M. Morari, M. Curatolo

SGAR - Schweizerische Gesellschaft fŁr Anesthesiologie und Reanimation, Annual Meeting, Fribourg, Switzerland, abstract

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limit on the potential combinations. Therefore, addressing the question of optimal drug dosing, one cannot avoid considering also side effects. METHODS: By extension of a previously published interaction model we propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patientís wellness is defined by superposition of positive and negative effects. Response surfaces for patientís wellness are constructed, their shape depending on the pharmacodynamic characteristics of the individual drugs and on their interaction type. Simulations are performed to test the effect of the different parameters on the shape of the wellness-surface. RESULTS: Combinations of drugs with different therapeutic ranges and interaction types can be simulated. Synergy in the positive effects as well as antagonism in the negative effects increase patientís wellness in opposition to antagonism in the positive and synergy in the side effects. The effect of the interaction parameters is valid for different relative shapes of the individual pharmacodynamics involved. CONCLUSIONS: We have presented a new method to include side effects in modeling of drug action for one or more drugs. The method allows for direct identification of optimal drug doses and represents an important step in developing guidelines for optimal drug dosing.


Type of Publication:


M. Curatolo

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% Autogenerated BibTeX entry
@InProceedings { ZanEtal:2004:IFA_1860,
    author={E. Zanderigo and V. Sartori and G. Sveticic and M. Morari and M.
    title={{A Model To Investigate Drug Interactions for Positive and
	  Adverse Effects}},
    booktitle={SGAR - Schweizerische Gesellschaft f{\"u}r Anesthesiologie
	  und Reanimation, Annual Meeting},
    address={Fribourg, Switzerland},
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