Ethnicity in Drug Development and Therapeutics

September 1, 2002

Applied Clinical Trials

A review of Edyta J. Frackiewicz, Thomas M. Shiovitz, and Stanford S. Jhee's clinical trial book.

Ethnicity in Drug Development and Therapeutics

Edyta J. Frackiewicz, Thomas M. Shiovitz, and Stanford S. Jhee (Greenwich Medical Media Ltd., London, 2002), 135 pages, hardcover, ISBN: 1-841101-27-3, $69.00.

In eight chapters, the authors present a brief overview, to both researchers and clinicians, of clinical evidence on the differences in responses to some medicines in various ethnic and racial groups. The book includes the pharmacokinetic aspect of differences; explanation of the basic genetic and non-genetic background for these differences; a brief overview of the ethnic element in clinical research; and the regulatory aspect of ethnic and racial difference in response to medicines.

The emphasis is on pharmacokinetics, presenting the differences in bioavailability, distribution, and elimination of drugs, with special attention given to the biotransformation of drugs. The book details the role of cytochrome P450, and to a lesser extent, non-cytochrome P450 enzymes, and their place in food-drug and drug-drug interactions. It includes a very useful list of drugs that inhibit or induce specific CYP isoforms. In describing the importance of different plasma concentrations of drugs, the authors very briefly describe a population pharmacokinetic model with ethnicity and race as covariates. The influence of environmental factors on intra-individual variability is also described, as is the way in which the effect of medicines is influenced.

In giving examples of inter-ethnic/interracial differences, the authors have mainly presented the mean values of various parameters, sometimes with standard deviations, but without confidence intervals or the size of sample from which the measurements were taken. It would be much easier to appreciate the extent of the differences if inter- and intra-subject variability were described. In some cases the differences identified were marginal and likely without clinical relevance, or were so small that they would have been lost within the range of inter-/intra-individual variability.

The book is too concise to enable a sufficiently accurate and detailed analysis of the processes involved, which could lead to some misunderstanding or misinterpretation. However, a very rich bibliography is provided for additional reading.

This book can be recommended to those who are new to this area. It gives a clear message of the importance of rational and individually tailored therapy, and of how crucial it is to take into account, when prescribing and developing drugs, how our genetic and ethnic differences can cause us to respond differently and variously to medicines. It is beyond the scope of this book to provide detailed explanations of all the comprehensive mechanisms involved in this very broad area, but it reiterates clearly that the time for a new approach is far overdue, especially in light of recent pharmacogenetic research and scientific advances.