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Disease and Acetylation Polymorphism

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Summary

Due in the main to a genetically determined difference in the activity of the liver N-acelyltransferase, a number of primary amine drugs or drug metabolites such as dapsone, isoniazid, hydrallazine, phenelzine, procainamide, sulphadimidine, sulphapyridine and nitrazepam are subject to a bimodal acetylation in man.

The population ratio of rapid versus slow acetylators varies widely between ethnic groups throughout the world, apparently being highest in those of an Eastern Asian origin and lowest in Egypt and some Western European countries. With some exceptions, the general clinical consequences of these differences in acetylator phenotype are, if any, that when patients are given a standard dose of the drugs mentioned, the slow acetylators are those who develop most adverse reactions while the rapid acetylators seem more prone to show an inadequate or lack of response to the standard dose.

The rationale behind dose adjustments based upon acetylator phenotyping is discussed, and it is tentatively concluded that more precise knowledge about the acetylator phenotype of the therapy. However, the possibility that a variety of pathophysiological factors and the concomitant therapy. However, the possibility that a variety of pathophysiological factors and the concomitant use of other drugs may interfere with acetylator phenotyping has to be considered, as well as some recent evidence that the acetylator phenotype may in itself represent a determinant for the development of certain diseases, like systemic lupus erythematosus and renal failure.

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  1. Division of Clinical Pharmacology and Toxicology, The Central Laboratory, Ullevaal Hospital, Oslo I, Norway

    Per Knut M. Lunde &  K. Frislid

  2. Division of Clinical Pharmacology and Toxicology, The Central Laboratory Medical Department VIII, Ullevaal Hospital, Oslo I, Norway

    V. Hansleen

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Lunde, P.K.M., Frislid, K. & Hansleen, V. Disease and Acetylation Polymorphism. Clin Pharmacokinet 2, 182–197 (1977). https://doi.org/10.2165/00003088-197702030-00003

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