Pharmacokinetics of Sulfonamides in Man

Vree, T. B.; Termond, E. F. S.

doi:10.1159/000410274

Cited by 21 publications

(55 citation statements)

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“…In man the renal clearance of SMZ is 0.25-2.5 ml/min/70 kg, thus at least 60 times lower than in cows (see Table 3). This lower SMZ renal clearance value in man can be explained by the low average urine flow (1 ml/min) and the tubular reabsorption of SMZ due to normally lower pH (ranging between 6 and 7) of human urine (14). In addition, the renal clearance of N4-SMZ in ruminants is eight times as high as in man.…”

Section: Metabolismmentioning

confidence: 95%

“…Blood (and milk) sampling occurred during 48 h and urine sampling during 12 h. SMZ and its metabolites 5-hydroxy-(SOH) and Neacetylsulphamethazole (N4-synthesised by Dr. Vree as described previously (14). Protein-binding studies and deglucuronidation of samples were carried out as described in earlier papers (9,10) The plasma sulphamethoxazole (SMZ) concentration-time curves could be * Plasma percentage of N4-SMZ versus SMZ in the final elimination phase analysed according to a two-compartment model.…”

Section: Methodsmentioning

confidence: 99%

“…Thus the methyl moiety blocks the hydroxylation and another specific P-450 isoenzyme is required for the hydroxylation of SMZ. It is noteworthy that in the homing pigeon and in turtles the hydroxylation pathway predominates that of acetylation (15,18). Thus species differences in hydroxylation may be explained by various types of P-450 isoenzymes in the liver, which determine the extent and rate of hydroxylation of a specific drug.…”

Section: Metabolismmentioning

confidence: 99%

“…Many studies have been carried out on its pharmacokinetic behaviour, metabolism and renal clearance in man, in relation to age and disease state, using specific high-performance liquid chromatography (HPLC) methods (14). In animals, however, this kind of information is limited.…”

Section: Introductionmentioning

confidence: 99%

“…In animals, however, this kind of information is limited. The reported elimination half-lives of sulphamethoxazole (SMZ) are varying (2,4,5,7,8,11,12,13,14); e.g., in man 9.5 h, in the dog 8 h, in the horse 5 h, in the cow 2.5 h, in the buffalo 7 h, in the pig 3 h, in sheep 2 h and in the cat 10 h. With respect to its metabolism, SMZ is predominantly acetylated in man, the penguin, the cat and sheep, but in the dog, the homing pigeon, the snail and the water turtle hydroxylation predominates (14,15,16,17,18).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of sulphamethoxazole in calves and cows

Nouws¹,

Vree

Degen³

et al. 1991

Veterinary Quarterly

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SUMMARY The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age-dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration-time curves of the N4-acetyl metabolite in the elimination phase were parallel to those of the parent drug; the No-acetyl metabolite plasma percentage depended on age and ranged between 100% (new-born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half-lives: 2.0-4.7 It) and exhibited a relatively small distribution volume ( f/Darea: 0.44-0.571/kg). SMZ was excreted predominantly by glomerular filtration, while its No-acetyl metabolite was actively eliminated by tubular secretion.

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Section: Metabolismmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacokinetics of sulphamethoxazole in calves and cows

Nouws¹,

Vree

Degen³

et al. 1991

Veterinary Quarterly

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Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man

Vree

Kolmer

1990

Pharmaceutisch Weekblad Scientific Edition

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Sulfadimethoxine is metabolized by O-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8 +/- 4.2 h versus 36.3 +/- 5.4 h; P = 0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3 +/- 5.2 h versus 53.5 +/- 8.5 h, P = 0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50-60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40-50% for excretion into bile and faeces.

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Trace Determination of Macrolide and Sulfonamide Antimicrobials, a Human Sulfonamide Metabolite, and Trimethoprim in Wastewater Using Liquid Chromatography Coupled to Electrospray Tandem Mass Spectrometry

et al. 2004

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An analytical method has been developed and validated for the simultaneous trace determination of four macrolide antibiotics, six sulfonamides, the human metabolite N4-acetylsulfamethoxazole, and trimethoprim in wastewater. The method was validated for tertiary, secondary, and-unlike in previously published methods-also for primary effluents of municipal wastewater treatment plants. This wide range of application is necessary to thoroughly investigate the occurrence and fate of chemicals in wastewater treatment. Wastewater samples were enriched by solid-phase extraction, followed by reversed-phase liquid chromatography coupled to tandem mass spectrometry using positive electrospray ionization. Recoveries from all sample matrixes were generally above 80%, and the combined measurement uncertainty varied between 2 and 18%. Concentrations measured in tertiary effluents ranged between 10 ng/L for roxithromycin and 423 ng/L for sulfamethoxazole. Corresponding levels in primary effluents varied from 22 to 1450 ng/L, respectively. Trace amounts of these emerging contaminants reach ambient waters, since all analytes were not fully eliminated during conventional activated sludge treatment followed by sand filtration. In the case of sulfamethoxazole, the amount present as human metabolite N4-acetylsulfamethoxazole had to be taken into account in order to correctly assess the fate of sulfamethoxazole in wastewater treatment.

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Pharmacokinetics of Sulfonamides in Man

Cited by 21 publications

References 0 publications

Pharmacokinetics of sulphamethoxazole in calves and cows

Pharmacokinetics of sulphamethoxazole in calves and cows

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man

Trace Determination of Macrolide and Sulfonamide Antimicrobials, a Human Sulfonamide Metabolite, and Trimethoprim in Wastewater Using Liquid Chromatography Coupled to Electrospray Tandem Mass Spectrometry

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