Taggart A J, McDermott B, Delargy M, Elborn S, Forbes J, Roberts S D, Ahnfelt N O
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Scand J Rheumatol Suppl. 1987;64:29-36. doi: 10.3109/03009748709096719.
The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.
对20例“活动期”类风湿关节炎患者进行急性和慢性给药后，研究了肠溶型柳氮磺胺吡啶（Salazopyrin - EN）的临床药代动力学。12名老年患者（平均年龄74.4±1岁；范围71 - 83岁）和8名年轻患者（平均年龄40.5±1.4岁；范围35 - 46岁）在禁食过夜后口服单剂量2g柳氮磺胺吡啶。在96小时内定期采集血清和尿液样本，以测定柳氮磺胺吡啶、磺胺吡啶及其代谢物的浓度。在连续17天每日服用2g Salazopyrin - EN进行治疗后，重复该过程，以比较药物在“稳态”时的动力学。虽然动力学参数的个体间差异很大，但年龄和乙酰化状态对一些因素有显著影响。老年患者中柳氮磺胺吡啶的消除半衰期延长，而在“稳态”时慢乙酰化者的肾清除率增加。单次给药后，老年患者中磺胺吡啶的达峰时间和表观分布容积增加，但这些差异在规律给药后消失。磺胺吡啶的峰浓度、消除半衰期、“稳态”血清浓度、表观分布容积和总清除率均受乙酰化状态影响。我们得出结论，老年对机体处理柳氮磺胺吡啶和磺胺吡啶的影响较小，但乙酰化表型在决定磺胺吡啶的“稳态”血清浓度方面起重要作用。这可能对该药物的一些不良反应具有实际意义。
