Acetylation of sulfamethazine in a Nigerian population

Abstract

Sulfamethazine (syn, sulfadimidine) is inactivated by conversion to its N-acetyl derivative. Individuals are phenotyped as either "rapid" or "slow" acetylators. We have tested the validity of this theory in a Nigerian population. The frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum were found to be bimodal, indicating the existence of a genetic polymorphism as observed by earlier workers. A plot of the percentage of the drug acetylated in serum against that in urine of the same individual results in a satisfactory separation of the rapid and slow acetylator phenotypes. An incidence of the slow acetylator phenotype of 41% was observed in the Nigerian population tested. How this observation fits into the hypothesis that the slow frequency of the allele increases from the Arctic Circle toward the Equator is discussed.

Evaluation of acetylator phenotype of isoniazid among tuberculosis patients in delta state Nigeria: update on management of toxicity

“…The reports indicated 41%-51% of slow acetylators were observed in Nigerian populations being treated with sulfamethazine, and highlighted a hypothesis that slow acetylator phenotype may be more prevalent in populations of people living nearer the Equator relative to the Arctic Circle. [32][33][34] While our report from the 1996 study was not in line with the hypothesis of more slow acetylators (i.e. given that Nigeria is nearer to the equator), the observation of a higher proportion of the subjects being fast acetylators corroborated with a West African study.…”

Polymorphic acetylation of sulphamethazine in a Zimbabwe population.

“…[1][2][3] Subjects are generally classified as slow or rapid acetylators46 and the proportion of slow to rapid acetylators varies among different peoples,7 but still exhibits bimodality even among regional groupings of a population.8 9 The present study was carried out to establish the existence of genetic polymorphism in a Zimbabwean population. The study also presents evidence that the determination of the acetylator phenotype using the method of Bratton and Marshall as given by Varley'1( can be achieved, even when the incubation time is reduced to 40 minutes and using a very small dose of sulphamethazine.…”

A gender wise study of arylamine N-acetyltransferase 2 (NAT2) acetylation phenotyping using sulphamethazine by high-pressure liquid chromatography (HPLC) assay

“…The distribution of slow acetylators was 14.6% among Indian pulmonary patients the Iranian population (Khalili et al, 2009) In Asians slow acetylator phenotype is much less frequent (10). In Nigerian population 41% slow acetylators were observed (Eze and Obidoa, 1978), in native Chinese population 19.8% slow acetylators were found after a single oral dose of 1 g Sulphamethazine (Xu and Jiang, 1990), similarly an apparent bimodal distribution of acetylator phenotype in 96 subjects (27% slow and 73% fast acetylators) was found from measuring the percentage of acetylation of sulphamethazine in 6 h plasma sample (Huang et al, 1992) which are similar to our findings as NAT 2 acetylation phenotype distribution in our study population was bimodal as 61 fast and 39% slow irrespective of gender. There was no significant χ 2 <3.832 difference of NAT 2 acetylation distribution in Plasm a AcSMZ/SMZ Plasma AcSMZ concentration (ug/ml) Plasma AcSMZ concentration (µg/ml) Figure 9.…”