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A New Drug Interaction Model: Application to Combination of Intravenous Morphine with Ketamine

Author(s):

V. Sartori, E. Zanderigo, G. Sveticic, T. Bouillon, P.M. Schumacher, M. Morari, M. Curatolo
Conference/Journal:

vol. AUT05-07
Abstract:

Background: According to a new model for drug interactions17, the patientsí well being, reflecting its global outcome after drug administration can be defined as the algebraic sum of positive and negative effects as a function of the concentrations of the drugs. This investigation aims at applying that model on a clinical question, the combination of intravenous morphine with ketamine and at showing its potential usefulness in identifying optimal drug therapeutic regimens. Methods: The pharmacodynamic parameters necessary to describe the well-being surface were found in the literature or estimated from available data. The interaction parameters were estimated using a novel procedure based on the data from a previous clinical study9. Results: The estimated values for the interaction parameters between morphine and ketamine are b = 2.5 for positive effect and bS = -3 for negative effects. According to those parameters the optimal effect compartment concentration range of morphine and ketamine was identified Conclusions: The proposed approach allowed for the estimation of the unknown interaction parameters between morphine and ketamine. This allowed for drawing the response surface for combination of intravenous morphine with ketamine and for identifying the optimal effect compartment concentrations range to be targeted during drug administration. The new framework could help exploring the issue of optimal drug combination in clinical practice.

Year:

2005
Type of Publication:

(04)Technical Report
Supervisor:

M. Curatolo

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% Autogenerated BibTeX entry
@TechReport { SarEtal:2005:IFA_2153,
    author={V. Sartori and E. Zanderigo and G. Sveticic and T. Bouillon and P.M.
	  Schumacher and M. Morari and M. Curatolo},
    title={{A New Drug Interaction Model: Application to Combination of
	  Intravenous Morphine with Ketamine}},
    institution={},
    year={2005},
    number={},
    address={},
    month=mar,
    url={http://control.ee.ethz.ch/index.cgi?page=publications;action=details;id=2153}
}
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