Exploiting race in drug development: BiDil's interim model of pharmacogenomics.

This paper explores events surrounding the US Food and Drug Administration's formal approval of the heart failure drug BiDil in 2005. BiDil is the first drug ever to be approved with a race-specific indication, in this case to treat heart failure in 'self-identified black patients'. BiDil has been cast by many as a step toward the promised land of individualized pharmacogenomic therapies. This paper argues, however, that when examined in context, the approval of BiDil emerges as a new model of how a pharmaceutical company may exploit race in the marketplace by literally capitalizing on the racial identity of minority populations and leveraging the disproportionate risk of adverse health outcomes they suffer into a cheaper, more efficient way to gain the US Food and Drug Administration's approval for drugs. Discussions of BiDil in both popular media and professional journals have repeatedly elided the difference between pharmacogenomic and race-based medicine. In fact, broad-based true pharmacogenomic therapies remain years-perhaps decades-in the future. The story of BiDil's development elucidates an alternative model to developing tailored therapies that promises to fill in the gap between the promise and reality of pharmacogenomic medicine. It is a model that exploits race to gain regulatory and commercial advantage, while ignoring its power to promote a regeneticization of racial categories in society at large.

Historical aspects of nitrate therapy.

The exciting story of the development of nitrates as drugs in clinical medicine is briefly reviewed. Glyceryl trinitrate (nitroglycerin) was synthesised by Sombrero in 1847. Amyl nitrite was discovered a few years later and was used by Guthrie in 1859. The first report on the action of glyceryl trinitrate and amyl nitrite was published by Brunton in 1867, and further papers were published by Murell in 1879. Organic nitrates appeared in the 1930s. Krantz and co-workers synthesised and used mannide dinitrate, which was longer acting than the nitrates that had been used previously. Research on a similar drug, isosorbide dinitrate, was initiated by Porjé in Stockholm. The drug was first marketed in Sweden in 1946. Isosorbide dinitrate was independently synthesised in the United States by Harris and colleagues in the 1950s. The drug was used fairly extensively on both sides of the Atlantic. However, there was a temporary decrease in popularity around 1970 when Needleman and colleages reported oral nitrates to be of questionable value, as they underwent rapid biotransformation during first-pass metabolism in the liver. This opinion was later altered and today the drug enjoys worldwide acceptance in different formulations. Also, in recent years one of the active metabolites, isosorbide 5-mononitrate, has been marketed as an effective antianginal drug.

History of the synthesis and pharmacology of isosorbide dinitrate.

A major research program in the University of Maryland School of Medicine, Department of Pharmacology, in the 1930s was the preparation of a large number of sugar alcohols and their anhydrides as substitute carbohydrates for diabetic diets. As an outgrowth of this work, many of these polyols were converted to their nitrate esters and investigated for their vasodilating properties. The organic nitrates that were synthesized were examined for their potency, duration of action, and possible therapeutic use. It was demonstrated that, contrary to prior belief, the depressor and vasodilating action was exhibited by their own molecular structure and not through hydrolysis and reduction to nitrite. The search for the finer mechanism(s) of action on the vascular musculature showed that these nitrated polyols and their anhydrides inhibited arterial adenosine triphosphatase, although this enzyme inhibition did not correlate with pharmacologic activity. Today the mechanism of action of these drugs is not clearly understood at the cellular level. The 1,4:3,6-dianhydrosorbitol 2,5-dinitrate (isosorbide dinitrate) was synthesized, studied, and reported in 1940. It appeared to be a useful drug because blood levels of the unhydrolyzed ester were found to persist for long periods of time. Subsequent clinical studies in the 1960s demonstrated its prophylactic value in angina pectoris and its prolonged action as a therapeutic asset. In 1967 the mononitrate was shown to be formed in vivo when the dinitrate was administered orally and has been studied as the possible pharmacodynamically active moiety.(ABSTRACT TRUNCATED AT 250 WORDS)