It makes no sense to develop new treatments among populations of patients who are different from those who will be using them. (1) Results from non-representative studies are not generalizable for several reasons. Broadly speaking, people of different races, ethnicities, genders, ages, and socioeconomic groups may have different pharmacogenetic (genetic variations in metabolic pathways), pharmacodynamic (what a drug does to the body), and pharmacokinetic (what the body does to a drug) responses to treatments.
For example, substantial numbers of African Americans are likely to be poor metabolizers of some psychotropic medications. Most psychotropic drugs are metabolized by one of the hepatic cytochrome P450 (CYP) isoenzymes. These isoenzymes can vary significantly depending on genetic background, and about 33% of blacks have a gene alteration in one of them, IID6, which slows the metabolism of tricyclic antidepressants. Likewise, approximately 20% of African Americans have a similar alteration in another CYP isoenzyme, IIC19, which helps process benzodiazepines. The slower metabolism of these medications can lead to higher plasma levels of the drugs, affecting their efficacy, toxicity, dosage, and number and severity of side effects. (2) In fact, research shows that genes in the CYP family mediate more than 75% of the phase Idependent metabolism of clinically used drugs (3), potentially altering responses to treatment.
Due to these variations and other factors, many common medications may be metabolized differently by diverse populations, and their effects may therefore be altered. Some of these medications include:
While race is, at best, an inexact indicator of differences in drug metabolism, inclusion of different races in statistically significant numbers can provide valuable information to clinical researchers in terms of possible responses.
References:
1.Increasing Minority Participation in Clinical Research: A White Paper from the Endocrine Society. December 2007.
2.Strickland, T, et al. The pharmacologic treatment of anxiety and depression in African Americans. Archives of Family Medicine. (1997); July-August 6(4).
3.Ng, P, et al. Individualized genomes instead of race for personalized medicine. Clinical Pharmacology & Therapeutics (2008); 84(3).
4.Shen, A, Chen, W, et al. Effect of Race/Ethnicity on the Efficacy of Warfarin: Potential Implications for Prevention of Stroke in Patients with Atrial Fibrillation. CNS Drugs.(2008) 22:10.
5.Urban, T. Race, ethnicity, ancestry, and pharmacogenetics. Mt. Sinai Journal of Medicine. (2010) 77:133-139.