Pharmacokinetics and acetylation of sulfa-2-monomethoxine in humans.
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).
Vree
T B
TB
Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint-Radboud, The Netherlands.
Beneken Kolmer
W J
WJ
Hekster
Y A
YA
Shimoda
M
M
Ono
M
M
Miura
T
T
D000107:Acetylation; D000328:Adult; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011485:Protein Binding; D012044:Regression Analysis; D013422:Sulfamonomethoxine / Q000378:metabolism / Q000493:pharmacokinetics*
D013422:Sulfamonomethoxine