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Predicting the impact of an ineffective enzyme on a drug’s Alain Li-Wan-Po
action is difficult for a body that has evolved over millions
of years. Secondly, the relationships between dose and than to go one step back to a defective genetic variant.
blood level, and blood level and activity are complex. It is That is why with warfarin, measuring blood clotting (INR;
usually better to measure blood level than to predict it International Normalised Ratio) is better than using
from the genetic variants, particularly for drugs with genetic algorithms. Well over one hundred studies have
narrow therapeutic windows. That is why for drugs such as shown this. In any case, new drugs that are easier to use
vancomycin and tacrolimus, therapeutic blood level than warfarin are available. One day costs will come down
monitoring is still the best optimizer. Thirdly, when a to make them more affordable and perhaps make warfarin
pharmacodynamic effect or biomarker of beneficial or obsolete.
adverse effect is measurable it is usually better to use it
Fourth, the road from drug to action is long and
winding. For example, over one hundred genes are said to
be involved in the action and disposition of warfarin.
Figure 2. Processing and function of microRNAs.
EPIGENETICS AND AN EXPANDING RNA change in DNA sequence, initially applied to the study of
embryonic development, now provides considerable
WORLD insight into the action of drugs, including drug resistance.
The study of epigenesis, or the study of the functional We know now that the bases that make up DNA are often
impact of DNA modifications that do not involve any
96 @Real Academia Nacional de Farmacia. Spain
