Some drugs behave differently in different people and some of this variation is due to genes.
As we characterise and become ready to identify more of these genes, the prospect of avoiding ineffective or dangerous therapies for an individual, while choosing the drug and dose most suited to him becomes increasingly credible.
Politics may start to get in the way, as our present knowledge more often allows us to predict what agents are most effective for a given condition in some human subpopulations. This has caused major controversy as with drugs only licensed for American Blacks, . And we are only talking here about two old drugs, isosorbide dinitrate and hydrallazine. More recently rosuvastatin dosage advice was altered downwards in the European Union in those of Asian stock, as drug levels for a given dose are about twice as high than whites in those of Chinese, Malay, and Asian-Indian ancestory . This effect seems to be polygenetic, in the sense that a candidate genetic polymorphism that seemed to explain the issue in the Japanese did not do so in these other groups. Such issues make individual prediction of drug metabolism more an art than a science. Indeed much challenging drug toxicity can be related to the issue that it is hard for doctors to retain all the information already known about risks of toxicity as the scientific information is observational rather than 100% predictive from first principles in most cases. None the less understanding the principles of pharmacogenetic polymorphisms is essential for those interested in drug toxicity and the rational design of drugs and is likely to become essential for individually tailored drug therapy based on genotype which may not be that far away. This may remove the political issues but could raise some individual issues which may have medico-legal implications.
An example is dual blockade of the Renin-Angiotensin-Aldosterone system using ARB and ACEI together. Determining the ACE/ID genotype may help identify patients particularly sensitive to such therapy. The anti-proteinuric effect of dual RAS blockade is influenced by the insertion(I)/deletion(D) polymorphism in the ACE gene. Needs citation
- ↑ http://www.washingtonpost.com/wp-dyn/content/article/2005/06/23/AR2005062301762.html
- ↑ Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005;78(4):330-41.