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Oral presentation

There is increasing knowledge on the genetic background of interethnic differences of drug bioavailability but also of drug response. However, extrinsic factors may also influence the phenotype of individuals. E.g. it is known that dietary factors may alter the metabolism of defined drugs, metabolized by CYP2D6, since it could be shown that e.g. Ethiopians living in Ethiopia have lower metabolic rations of debrisoquine compared to Ethiopians living in Sweden. On the other hand, there is clear evidence that particularly this ethnic group comprises the highest frequency of CYP2D6 ultrarapid metabolizers world-wide. This example shows that the genetic background but also environmental factors such as climate, socio-economy, educational status, food habits, and moreover different definitions of disease and therapeutic approaches are particularly difficult to quantify and may cause considerable differences in drug safety, efficacy, dosage, or dose regimen.

One approach to assess the likelihood of interethnic differences of a given drug may be the preclinical investigation of the metabolic pathway, binding to polymorphic receptors or ion-channels, and moreover, investigations towards interactions with environmental compounds.

Polymorphic drug metabolizing enzymes such as cytochrome P450 2D6, 2C9, 2C19 or arylamine N-acetyltransferases have been intensively characterized and genotyped in numerous populations. In the recent time, however, drug transporters such as P-glycoprotein encoded by MDR1 ran into focus, since there were promising studies showing a remarkable influence of genetic variants on drug bioavailability of digoxin or HIV protease inhibitors in Caucasian Whites. Though, the results are conflicting and there is an ongoing discussion about the significance of pharmacogenetics on drug transporters in different ethnicities.

It should be taken also into account that aside different pharmacokinetics, the efficacy may be affected by hereditary variants in receptors e.g. β-adrenoreceptors. Therefore, the approach to recommend the drug dosage simply based on an individual's genotype requires the knowledge on the possible influence of genetic variants on the bioavailability and drug response. However, prospective studies are lacking for most of drugs available.

Currently, it is still a big challenge to assess all ethnical factors influencing drug therapy. During drug-development, however, one has to focus on the major factors, which underlie genetic control such as polymorphic cytochrome P450s, since consideration of these factors may significantly reduce the variability of pharmacokinetics within a given study population.

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