ABSTRACT
Advances in drug design and development have brought about substantial improvements in the clinical management of patients. However, not all individuals benefit from pharmacological intervention as some fail to respond satisfactorily while others develop side effects that impair the overall success of treatment. This variable outcome is widely recognized as a significant problem throughout clinical practice. Its reasons began to be better understood in the 1950s, when the relation between inherited differences among individuals and therapeutic outcome was identified. During this period researchers first described the association between prolonged muscle relaxation after suxamethonium administration and an inherited deficiency in plasma cholinesterase,1 and linked haemolysis during antimalarial treatment to inherited levels of the enzyme glucose 6phosphate dehydrogenase.2 The clinical implications of these discoveries heralded the inception of pharmacogenetics, and led to early studies examining the influence of genetic polymorphisms on enzyme activity, and determining how these relate to the therapeutic effects of clinical compounds.
