Vree T B, Beneken Kolmer W J, Hekster Y A, Shimoda M, Ono M, Miura T
Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint-Radboud, The Netherlands.
Biopharm Drug Dispos. 1992 Jan;13(1):55-68. doi: 10.1002/bdd.2510130105.
In humans sulfa-2-monomethoxine (S) is metabolized by N4-acetylation (39.9 +/- 8.0 per cent). After an oral dose, S is eliminated biphasically (t1/2, 5.2 +/- 1.6 h and 13.2 +/- 3.4 h) which is similar in both fast and slow acetylators. The metabolite N4-acetylsulfa-2-monomethoxine (N4) is eliminated monophasically (t1/2, 30.0 +/- 5.7 h). The intrinsic mean residence time (MRT) of N4 is 33.5 +/- 8.8 h. The mean total body clearance of S is 11.6 +/- 2.7 ml min-1, and the Vdss is 12.3 +/- 1.01. The renal clearance of S during the first day was twice as high as on the following days for two of the six volunteers (8 vs 4 ml min-1). The renal clearance of N4 during the first day, for four out of the six volunteers, was twice as high as on the following days (8 vs 4 ml min-1). The protein binding of S is 95 per cent and that of its conjugate N4 98 per cent. Approximately 80 per cent of the oral dose of S is excreted in the urine as parent drug (41.0 +/- 6.2 per cent) and as N4 acetyl conjugate (39.9 +/- 8.0 per cent).
在人体内，磺胺-2-甲氧基嘧啶（S）通过N4-乙酰化进行代谢（39.9±8.0%）。口服给药后，S以双相方式消除（t1/2分别为5.2±1.6小时和13.2±3.4小时），快速和慢速乙酰化者的情况相似。代谢产物N4-乙酰磺胺-2-甲氧基嘧啶（N4）以单相方式消除（t1/2为30.0±5.7小时）。N4的内在平均驻留时间（MRT）为33.5±8.8小时。S的平均全身清除率为11.6±2.7毫升/分钟，稳态分布容积为12.3±1.01。六名志愿者中有两名，第一天S的肾清除率是随后几天的两倍（8对4毫升/分钟）。六名志愿者中有四名，第一天N4的肾清除率是随后几天的两倍（8对4毫升/分钟）。S的蛋白结合率为95%，其共轭物N4的蛋白结合率为98%。口服剂量的S约80%以母体药物（41.0±6.2%）和N4乙酰共轭物（39.9±8.0%）的形式经尿液排泄。
