Cytochrome P450 enzyme polymorphisms and adverse drug reactions

Adverse drug reactions (ADR) are common and many are thought to have a genetic predisposition. There has been a great deal of interest in the role of P450 enzyme gene polymorphisms in the pathogenesis of adverse reactions. The major impact to date of polymorphic P450 expression has been on pre-clinical drug development. However, the direct clinical impact of P450 polymorphisms on prediction of ADRs has been limited, largely because studies have been small and retrospective, and the literature shows an abundance of contradictory data. Furthermore, the clinical- and cost-effectiveness of pre-prescription genotyping for P450 polymorphisms has not been convincingly demonstrated. Further studies that address these deficiencies are urgently needed--only then will prospective P450 genotyping become routine in clinical practice.