Pullar T, Hunter J A, Capell H A
Ann Rheum Dis. 1985 Dec;44(12):831-7. doi: 10.1136/ard.44.12.831.
A group of 54 patients with rheumatoid arthritis (31 fast, 23 slow acetylators) treated with sulphasalazine 3 g/day were studied retrospectively. At 24 weeks no difference in the efficacy of the drug could be shown between fast and slow acetylators. In a second prospective study 40 fast acetylators were allocated to 3 g/day and 20 slow acetylators to 1.5 g/day. At 24 weeks marked improvement was seen in the fast acetylators given high dose but not the slow acetylators given low dose. It was also noted in this study that the usual ratio of fast : slow acetylators was reversed, and there is some suggestion that fast acetylators may be predisposed to more severe rheumatoid arthritis. The toxicity pattern in a total of 149 patients (83 fast, 66 slow acetylators) was also studied. Significantly more slow acetylators stopped treatment because of nausea or vomiting, or both, but serious toxicity was not confined to either group. Acetylator phenotype therefore appears important in determining the incidence of nausea and/or vomiting associated with sulphasalazine therapy in patients with rheumatoid arthritis but has no effect on the occurrence of potentially serious toxicity or efficacy. Thus prior measurement of acetylator phenotype in patients with rheumatoid arthritis confers little practical benefit in their management.
对一组54例类风湿性关节炎患者（31例快乙酰化者，23例慢乙酰化者）进行回顾性研究，这些患者接受每日3克柳氮磺胺吡啶治疗。24周时，快乙酰化者和慢乙酰化者之间未显示出药物疗效的差异。在第二项前瞻性研究中，40例快乙酰化者被分配接受每日3克的剂量，20例慢乙酰化者被分配接受每日1.5克的剂量。24周时，接受高剂量的快乙酰化者有明显改善，而接受低剂量的慢乙酰化者则没有。该研究还指出，快乙酰化者与慢乙酰化者的通常比例发生了逆转，并且有迹象表明快乙酰化者可能更容易患更严重的类风湿性关节炎。还对总共149例患者（83例快乙酰化者，66例慢乙酰化者）的毒性模式进行了研究。因恶心或呕吐或两者而停止治疗的慢乙酰化者明显更多，但严重毒性并不局限于任何一组。因此，乙酰化者表型在确定类风湿性关节炎患者柳氮磺胺吡啶治疗相关恶心和/或呕吐的发生率方面似乎很重要，但对潜在严重毒性或疗效的发生没有影响。因此，对类风湿性关节炎患者预先测量乙酰化者表型在其治疗管理中几乎没有实际益处。
