Irshaid Y M, al-Hadidi H F, Abuirjeie M A, Rawashdeh N M, Gharaibeh N S
Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid.
Int J Clin Pharmacol Ther Toxicol. 1993 Jan;31(1):18-22.
We studied the acetylation of dapsone (DDS) in vitro by whole blood taken from subjects with known acetylator phenotype. The acetylation of DDS by whole blood was both incubation time- and DDS concentration-dependent. Thus, it is highly recommended to separate plasma immediately after blood withdrawal during acetylation phenotyping using DDS. para-aminobenzoic acid (PABA) substantially inhibited the acetylation of DDS by whole blood taken from both slow and rapid acetylators, while procainamide (PAD) significantly inhibited DDS acetylation by whole blood taken from slow acetylators. At the highest PAD concentration used (208 microM), DDS acetylation by whole blood taken from rapid acetylators was also inhibited. In contrast, sulphanilamide (SAD) failed to produce any significant inhibition of the acetylation of DDS by whole blood taken from either slow or rapid acetylators. Furthermore, there was no correlation between DDS acetylation by whole blood in vitro and the acetylator status of the subject. It is therefore not possible to predict the acetylator phenotype by studying DDS acetylation by human whole blood. These results indicate that the DDS N-acetyltransferase of human whole blood is most probably of the monomorphic type.
我们利用已知乙酰化表型受试者的全血，在体外研究了氨苯砜（DDS）的乙酰化作用。全血对DDS的乙酰化作用既依赖于孵育时间，也依赖于DDS浓度。因此，强烈建议在使用DDS进行乙酰化表型分析时，采血后立即分离血浆。对氨基苯甲酸（PABA）能显著抑制慢乙酰化者和快乙酰化者全血对DDS的乙酰化作用，而普鲁卡因酰胺（PAD）能显著抑制慢乙酰化者全血对DDS的乙酰化作用。在所用的最高PAD浓度（208微摩尔）时，快乙酰化者全血对DDS的乙酰化作用也受到抑制。相比之下，磺胺（SAD）未能对慢乙酰化者或快乙酰化者全血对DDS的乙酰化作用产生任何显著抑制。此外，体外全血对DDS的乙酰化作用与受试者的乙酰化状态之间没有相关性。因此，不可能通过研究人全血对DDS的乙酰化作用来预测乙酰化表型。这些结果表明，人全血的DDS N - 乙酰转移酶很可能是单态型的。
