Slow acetylator

The detoxification of drugs and xenobiotics by acetylation in the human organism is catalysed by the N-acetyltransferases (NAT) NAT1 and NAT2. The acetylation phenotype of a human being is genetically determined.

Slow acetylation (opposite: fast acetylation) is the term used to describe persons who, due to their special enzyme equipment, can only slowly biotransform certain drugs (e.g. sulfonamides, nitrazepam, isoniazid) through acetylation. This applies to 40-70% of Europeans, 90% of North Africans and 10% of Japanese and Chinese.

For example, people who acetylate isoniazid quickly have a plasma concentration of only 1 μg/ml 6 hours after taking 9.8 mg of substance per kg body weight. Slow acetylators still have 4-5 times the level of isoniazid in plasma during the same period.

The phenotype of the "slow acetylator" (SA) is caused by homozygous or combined heterozygous variants in the coding region of the NAT2 gene. 4 variant alleles (NAT2*5a/b, *6a, *7a/b, *14a) are particularly common. NAT2-related adverse drug reactions (ADRs) lead to polyneuropathy or hypersensitivity to sulfonamides in "slow acetylators".

Also relevant is the acetylation behaviour in contact with specific carcinogens, primarily the aromatic compounds such as nitrobenzene, aniline, dinitrotoluene and amino compounds of benzene.

It is known that bladder cancer caused by the substances benzidine, 4-aminodiphenyl and 2-naphthylamine occurs significantly more frequently in slow acetylators. Gastric non-cardiac adenocarcinoma (-GNA-) also occurs more frequently in slow acetylators than in a control group.

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