Ethnic differences in reactions to drugs and xenobiotics. Caffeine and other drugs.

I have presented some diverse case reports which illustrate several variations on the theme of this conference. A study of caffeine metabolites revealed two kinds of interethnic variation, one pertaining to the well-known acetylation polymorphism affecting the secondary metabolism of the parent drug; the other consisted of a difference in paraxanthine excretion which might indicate an ethnic difference in renal function. Older data on the pharmacokinetics of the antihistaminic drug diphenhydramine also suggested interethnic variables in the fate of the drug which do not necessarily involve metabolizing capacity. In short, pharmacokinetic factors other than metabolism may make additional contributions to ethnic differences in drug response. Studies of taste and smell are not only models of receptor variability but they may be used to reveal underlying biochemical differences. Furthermore, a polymorphism in tasting ability constituted an epidemiological risk factor for thyroid disease which was greatly enhanced in the presence of an appropriate human leukocyte antigen (HLA, histocompatibility gene). It is clear that the HLA complex will have to be increasingly considered in relation to pharmacological responses. Variabilities of superoxide dismutase and of various enzymes involved in heme production were described briefly because of their inherent or historical interest. In each case, however, the occurrence of variants was confined to small population groups as an expression of founder effects and regional polymorphism. Several other instances of ethnic differences in drug response were merely cited.