Pharmacogenetics differences

Choudhry S, Ung N, Avila PC, et al. (2005) Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med. 171, 563-570. 

It is self-evident that biotransformation will be reduced in patients with liver or kidney disease, in the elderly and also in neonates. In addition, pharmacogenetic differences play a considerable role in the way an individual patient metabolizes a drug. Such differences often result from polymorphisms in the cytochrome P450 family of microsomal enzymes. 

The average biological half-life of both drugs in man is comparatively long—in the region of 1-2 days—but large pharmacogenetic differences in... 

Genetic factors that influence enzyme levels account for some of these differences. Succinylcholine, for example, is metabolized only half as rapidly in persons with genetically determined defects in pseudocholinesterase as in persons with normally functioning pseudocholinesterase. Analogous pharmacogenetic differences are seen in the acetylation of isoniazid (Figure 4-5) and the hydroxylation of warfarin. The defect in slow acetylators (of isoniazid and similar amines) appears to be caused by the synthesis of less of the enzyme rather than of an abnormal form of it. Inherited as an autosomal recessive trait, the slow acetylator phenotype occurs in about 50% of blacks and... 

It is largely a matter of economic and cultural factors that we know more about pharmacogenetic differences between Caucasian and Asian populations than between these and African populations. Data obtained with African-Americans must be interpreted as having a Caucasian admixture of approximately 30% African populations are not a uniform group and often differ substantially from one another. 

Whenever inter-individual pharmacogenetic differences are observed, a proper search usually showed the existence of equivalent interethnic differences. It is not entirely clear whether this rule applies specifically to pharmacogenetics, or whether it affects all genetic variations to the same extent. 

Acetylation exhibits a well-known pharmacogenetic difference in the human population that is bimodal (fast or slow) and perhaps even trimodal. This difference accounts for the greater toxicity of certain drugs in either fast or slow acetylators, depending on whether the parent drug or its acetyl derivative is the more toxic entity. 

Pharmacogenetic differences in the metabolism of clomipramine after a single oral dose are apparent as increased plasma clomipramine concentrations in Indian and Pakistani patients compared with Caucasians. In Japanese patients, substantial interindividual variation in demethylation and hydroxylation of clomipramine was observed, although the prevalence of poor demethylators and poor hydroxylators of clomipramine has been estimated to be less than 1%. 

Pharmacogenetics began with the observation of interindividual differences of some drug responses or of drug metabolism that started pharmacogenetics. This recognition, that there are pharmacogenetic differences between populations, truly widened and altered the science. Various older observations that... 

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