Pharmacokinetics and acetylation of sulfa‐2‐monomethoxine in humans

Abstract

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).

Direct measurement of probenecid and its glucuronide conjugate by means of high pressure liquid chromatography in plasma and urine of humans

“…This method is comparable to those already published by this group, e.g. oxazepam glucuronide, temazepam glucuronide [24], codeine-6-glucuronide [25], 5-hydroxysulfapyridine glucuronide [26], sulfadimethoxine-Nl-glucuronide [27], sulfa-6-monomethoxine-N l-glucuronide [28], sulfamethomidine-Nl-glucuronide [29], sulfaphenazole-N2-glucuronide [30], and p-hydroxyphenylphenylhydantoine glucuronide [31].…”

Comparison of the metabolism of four sulphonamides between humans and pigs

“…Recently we were able to measure the N1-glucuronide conjugate of sulphadimethoxine and of sulfa-6-monomethoxine in the urine of man (10,12), but we were unable to find this metabolite in the urine of pigs (6). Instead sulphadimethoxine was completely N4-acetylated.…”

“…The parent drug elicits extremely low renal clearance values, suggesting tubular reabsorption. This reabsorption process, followed by N1-glucuronidation, is then a relatively slow process, resulting in the almost identical long half-lives for sulpha-2,6-dimethoxine, sulphamethomidine and sulpha-6-monomethoxine (10,12,17). The reabsorption can be assumed to be carried out by the urate reabsorption pathway, because sulpha-2,6-dimethoxine and urate have some similarities in their molecular structures.…”

O‐dealkylation and N4‐acetylation of sulpha‐2‐monomethoxine by the turtlePseudemys scripta elegans

“…The capacity factors of the compounds are respectively: sulpha-2-monomethoxine 4.86, N4-acetylsulpha-2-monomethoxine 6.54, and the unidentified compound at 2.91. Deconjugation Deglucuronidation was carried out by incubating for 6 hours at 37° C using 100 ill tank water, 100 ill of B-glucuronidase (50,000 U/ml type LII, lyophilised powder from limpets Patella vulgata) and 800 Al of potassium dihydrogen phosphate buffer, pH 3.8 (16,17).…”