Ethnic differences in risks of adverse reactions

Editor—McDowell et al conclude that patients from different ethnic groups have different risks for important adverse drug reactions on the basis of a meta-analysis of adverse reactions due to drugs used in cardiovascular medicine.¹ Data are sparse, and regulators should ask for better data before licensing.

Figure 1.

The use of pharmacokinetic and pharmacodynamic modelling would greatly facilitate this process. The European Commission sponsored a workshop to facilitate the incorporation of such modelling studies into drug development. Data from 1997 on naratriptan, a serotonin agonist treatment for acute migraine, used a population approach and Bayesian predictions to examine the pharmacokinetic and pharmacodynamic relations for oral naratriptan during phase II clinical trials.² Hepatic clearance of naratriptan declined with age and use of hormone contraception, potentially increasing the likelihood of adverse events leading to product labelling restrictions for elderly patients and leading to higher efficacy in women.³ In tobacco smokers and black patients the hepatic clearance was increased, leading to lower exposure to naratriptan.

A population based, pharmacokinetic and pharmacodynamic approach as exemplified by naratriptan should be encouraged as a routine component of early human drug development, which could predict the need for special precautions and potential adverse events arising from differing circulating drug concentrations arising from environmental factors (such as smoking), ageing, and ethnicity.