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Kinetic modelling of isometamidium chloride (Samorin) uptake by Trypanosoma congolense

Published online by Cambridge University Press:  06 April 2009

I. A. Sutherland ,
A. Mounsey ,
M. Eisler  and
P. H. Holmes
I. A. Sutherland
Affiliation:
Department of Veterinary Physiology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, Scotland
A. Mounsey
Affiliation:
Department of Veterinary Physiology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, Scotland
M. Eisler
Affiliation:
Department of Veterinary Physiology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, Scotland
P. H. Holmes
Affiliation:
Department of Veterinary Physiology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, Scotland
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Extract

Clones of Trypanosoma congolense which express resistance to the widely used trypanocide isometamidium chloride accumulate less of the drug than clones which are sensitive to drug treatment. A mathematical model has been developed which was able to predict theoretical lines representing the uptake kinetics in trypanosomes which were sensitive to isometamidium, as well as for resistant trypanosomes in which reduced accumulation was a result of either reduced uptake or enhanced efflux of the drug. Data from drug uptake experiments were then fitted to these theoretical lines. While the value for drug efflux could not be separated from the dissociation constant of the trypanosomes for isometamidium, it was demonstrated that reduced accumulation is not a result of reduced uptake of isometamidium by drug-resistant trypanosomes.

Keywords

Trypanosoma congolensedrug resistancekinetic modellingdrug efflux.
Type
Research Article
Information
Parasitology , Volume 105 , Issue 1 , August 1992 , pp. 91 - 95
Copyright
Copyright © Cambridge University Press 1992

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