Drug Balanced polymorphism

Furthermore, it has been observed that placental PGP is of great importance in limiting the fetal penetration of various potentially harmful or therapeutic compounds [64]. High PGP levels may have a role in the protection of fetuses from harmful tropical plant metabolites (from which many drugs are derived). An originally balanced polymorphism may have been preferentially selected by improved prenatal growth and development as well as improved postnatal health. This selective pressure may maintain the C allele in populations of African descent. 

Drug-sensitive hemolytic anemia is a hereditary disease, transmitted by a sex-linked dominant trait with low penetrance. The disease is widely distributed, and it is estimated that at least one hundred million people are affected by it. The anemia has been observed among many groups including Negroes, Jews, and Caucasians. It is prevalent in areas endemic for malaria. This association between malaria and drug-sensitive anemia results from a situation similar to that observed in sickle cell anemia, namely balanced polymorphism. 

Where drug are shown to form reactive intermediates by specific enzyme systems, it might be expected that the polymorphism or absence of these systems would track idiosyncratic reactions but to date no such link has been established. In fact, the most confounding element of idiosyncratic reactions is their unpredictable nature and whilst reactive intermediates may present a risk factor the true nature of the response is likely to be multifactorial. Changes in dmg metabolizing capacity, affecting the balance of bioactivation and bioinactivation processes which may be mediated through concomitant infection may also be a contributory factor. 

So, how diligently should we study the polymorphism of a potential new drug How many experiments should we conduct Virtually every pharmaceutical company has a different answer to these questions ranging from none to as many as possible. The following discussion is the author s opinion - attempting to strike a balance between extremes. 

DNA polymorphisms. The authors suggested that despite the risk of mortality associated with methadone-induced QT prolongation, the high mortality in untreated drug users tips the balance in favor of methadone. 

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