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Isobologram analysis

The benefit of combined therapies are being realised in the clinic. This has opened the door to a plethora of drug combinations being developed particularly for patients refractory to therapy. Resistant tumours may also be susceptible to combination therapies.

Whether or not a given drug combination works synergistically can be determined by isobologram analysis of data obtained from growth inhibition assays. The Loeweadditivity model (isobologram) is the most appropriate analysis for evaluating whether drugs are synergistic in their ability to kill tumour cells.

 

"Drugs that are given in combination may produce effects that are greater than or less than the effect predicted from their individual potencies. The historical basis for predicting the effect of a combination is based on the concept of dose equivalence; i.e., an equally effective dose (A) of one will add to the dose (B) of the other in the combination situation. For drugs with a constant relative potency, this leads to linear additive isoboles (A–B )curves of constant effect (line of additivity), whereas a varying potency ratio produces non-linear additive isoboles. Determination of the additive isobole is a necessary procedure for assessing both synergistic and antagonistic interactions of the combination." Tallarida JPET 319 (1): 1. (2006)

Through utilization of these analyses the optimal combination can be determined.

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