Best-in-class drugs

Freire E (2008) Do enthalpy and entropy distinguish first in class from best in class Drug Discov Today 13 869-874... 

As ADME/PK has become incorporated into drug discovery it has become necessary to reconsider the purpose of the studies. If the science is really going to reduce the attrition rate in development, then it is essential for the studies to allow predictions of the PK in man to be made. This means predicting the likely size and frequency of the dose. A review of the top 10 medicines of 1999 (Table 6.1) shows all of them to be once-a-day compounds. It is clear that to be best in class , and to be able to maintain that position as follow-up compounds come along, it seems probable that a compound will need to be suitable for once a day dosing. 

In summary it can be said that there are a lot of possibilities available to overcome the efflux pump-mediated absorption barrier in the intestinal tract. Further, more selective or more potent inhibitors will follow but it has to be carefully decided for each drug or therapy which type or class of inhibitor or efflux pump modulator might be best suited. Also drug delivery systems combining different efflux pump modulating properties have to be investigated in the future. 

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