Interethnic Differences in Drug Disposition and Response: Relevance for Drug Development, Licensing, and Registration

Abstract

In 1982, Kalow introduced his review on “Ethnic differences in drug metabolism” by stating that: “the literature contains a number of examples of differences between populations in drug metabolizing capacity. Although this topic has been discussed previously as part of pharmacogenetics review, it deserves a new effort with different emphasis on a recently expanded data base. The topic should help improve understanding of human biology, and is of practical significance in pharmacology and toxicology.” Ten years later the same statement is still true and considerable knowledge has been acquired at the molecular biology level. As a matter of fact, a recently published book on pharmacogenetics (Kalow 1992) contains important and extensive information on interethnic differences in drug metabolism. Accordingly, the authors of the present review decided to concentrate their presentation on aspects related essentially to drug development, licensing, and registration in the context of the new “4 W” environment (i.e., What and Why to present for World Wide drug registration). In this framework, pharmacokinetic/ pharmacodynamic (PK/PD) relationships are also becoming of importance, as exemplified by a recent conference (PECK et al. 1992), and the authors felt that their presentation should deal also with some aspects of interethnic differences in drug tolerance and response. However, the wide-ranging subject of interethnic differences in drug response and tolerance will not be discussed in detail in the present review and interested readers are referred to treatises of internal medicine such as the Harrison’s (Braunwald et al. 1988). Nevertheless, PK/PD relationships will serve as a reference framework for this chapter on interethnic differences in drug metabolism.KeywordsDrug MetabolismDrug DispositionAcetylator PhenotypeInterethnic DifferenceDrug BehaviorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.