Differences in Drug Response

Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada 

Attention to interethnic differences has become a major aspect of pharmacogenetics (1-9) stimulated by studies of drug response and toxicity in various human populations who differed in their response, even when taking usually well tolerated doses of some common therapeutic chemicals. The purpose of this chapter is to indicate essential elements of this broad topic, and to provide examples of some of its important aspects. 

In short, differences in drug response between human populations drew first attention 4 to 5 decades ago. However, because of the initial methodological shortcomings, the science of interethnic pharmacogenetics is in a strict sense only about 20 years old (10). 

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Evans WE, Johnson JA Pharmacogenomics the inherited basis for interindividual differences in drug response. Anna Rev Genomics Hum Genet 2001 2 9. 

Pharmacogenomics is the study of the inherited basis of interindividual differences in drug response. One approach is to search for genetic variants that are associated with severe adverse effects, which in turn can be used to screen for individuals who should not receive the drug in question or should receive an adjusted dose of the dmg. Another approach is to identify markers that predict dmg efficacy (2-4). 

Design of DNA microarrays lead to significant improvement in the field of pharmacogenomics, which deals with the reasons behind individual differences in drug responses, toxicity, and multiple drug resistance and hence, aims to find correlations between therapeutic responses to drugs and the genetic profiles of patients. 

Closer to the target of clinical effects are data obtained in humans. Here of course the problem of interspecies differences is avoided, but other problems become foremost. One of these is genetic differences between humans, with the discovery of genetic polymorphism in enzymes (Meyer et al., 1990) and receptors (Strange, 1994). Ethnopharmacology was born with the discovery that variations in genotypes and phenotypes between human populations are observed that cause many interethnic differences in drug responses (Kalow and Bertilsson, 1994). 

While this chapter aims to describe genetic factors which cause differences in drug response between human populations, one should not forget that population differences may also be caused by environmental influences. In... 

Thus, while most interethnic differences in drug response are now known to have a genetic basis, it would be wrong to assume automatically that there must be a genetic cause. 

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