Pharmacokinetics, Metabolism, and Renal Excretion of Sulfadimidine and Its N4-Acetyl and Hydroxy Metabolites in Humans

Vree, T. B.; Nouws, J. F. M.; Baakman, M.

doi:10.1097/00007691-198612000-00010

Cited by 18 publications

(11 citation statements)

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“…The half-life of elimination of sulfadimethoxine is smaller in fast acetylators than in slow acetylators (P = 0.013), while no differences in half-life can be observed between fast acetylators of Asian and of Caucasian origin (phenotype) (P = 0.338), as was observed for sulfadimidine [17]. The apparent half-life of the conjugate N4-acetylsulfadimethoxine is also smaller in fast than in slow acetylators (P = 0.036), but the calculated intrinsic mean residence time of the acetyl conjugate is similar in fast and slow acetylators (P = 0.556).…”

Section: Half-lifementioning

confidence: 79%

“…For instance, oxidation reactions have been demonstrated for sulfamethoxazole, sulfatroxazole, sulfadimidine and sulfamerazine in man, ruminants, reptiles and molluscs [14][15][16][17].In man, methoxysulfonamides, such as sulfadimethoxine, exhibit extremely long half-lives, a low percentage of N4-acetyl conjugation, a low percentage of renal excretion of parent drug and N4-acetyl conjugate, resulting in an incomplete mass balance (20%) [18 19]. This suggests that slowly performed oxidation reactions at the N1-substituent should be considered.…”

mentioning

confidence: 99%

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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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Section: Half-lifementioning

confidence: 79%

mentioning

confidence: 99%

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

Vree

Kolmer

1990

Pharmaceutisch Weekblad Scientific Edition

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“…Sulfamethazine is known to undergo metabolism to mainly form N 4 -acetyl-SM 2 in numerous species of domestic animals, including fish and humans (10)(11)(12)(13)(14). Metabolic alteration of the parent compound by fish to more polar species or to less polar species can have an impact upon bioconcentration (5), so N 4 -acetyl-SM 2 , which is less polar than SM 2 , was used as a biodegradation marker of the drug in the test organism.…”

Section: Introductionmentioning

confidence: 99%

Bioconcentration and Elimination of Sulfamethazine and Its Main Metabolite in Sturgeon (Acipenser schrenkii)

Hou

Shen²,

Zhang³

et al. 2003

J. Agric. Food Chem.

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A steady-state bioconcentration and elimination of sulfamethazine (SM2) in the sturgeon (A. schrenkii) was conducted in flow-through aqueous conditions. Two treated groups of fish were exposed to concentrations of 1.00 and 0.10 mg/L of SM2, respectively. SM2 and its main metabolite, N4-acetyl-SM2, were determined in both fish muscle and water during the 8-day uptake period and the subsequent 6-day elimination period. Rapid uptakes of the drug were observed in both treated groups. Muscle tissue residues plateaued after ∼3 days. The bioconcentration factor in muscle (BCFm) in the low-concentration drug solution was 1.19 and that in the high-concentration-treated level was 0.61. The calculated biodegradation index was 3.72%. The elimination half-times (t1/2) of the two treatment levels were 19.44 and 23.52 h, respectively. The result indicates that SM2 will neither bioconcentrate in individual aquatic organisms nor biomagnify in the food chain, although the BCFm was relatively higher under the low-concentration exposure. A steady-state bioconcentration and elimination of sulfamethazine (SM 2 ) in the sturgeon (A. schrenkii) was conducted in flow-through aqueous conditions. Two treated groups of fish were exposed to concentrations of 1.00 and 0.10 mg/L of SM 2 , respectively. SM 2 and its main metabolite, N 4 -acetyl-SM 2 , were determined in both fish muscle and water during the 8-day uptake period and the subsequent 6-day elimination period. Rapid uptakes of the drug were observed in both treated groups. Muscle tissue residues plateaued after ∼3 days. The bioconcentration factor in muscle (BCF m ) in the low-concentration drug solution was 1.19 and that in the high-concentration-treated level was 0.61. The calculated biodegradation index was 3.72%. The elimination half-times (t 1/2 ) of the two treatment levels were 19.44 and 23.52 h, respectively. The result indicates that SM 2 will neither bioconcentrate in individual aquatic organisms nor biomagnify in the food chain, although the BCF m was relatively higher under the low-concentration exposure.

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“…; Sun, Liu, Qin, Zhang, Xing, Xu & Gao ; Wang, Ji, Li, Guo, Xing & Chang ). The differences can be explained by the different acetylation ratio of sulpha drugs in different species, for example, fish exhibits a higher acetylation capacity to sulpha drugs than crustaceans, and the reported species‐specific acetylation ratios of sulpha drugs are 88%, 62.1%, 2% and 0% in human, Australian lepores album , Cyprinus carpio and Fenneropenaeus chinensis respectively (Grondel, Nouws & Haenen ; Vree, Hekster, Nouws & Baakman ; Yuan & Fung ; Zhang et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas, the observation of sulpha drugs accumulating in liver at a lower rate than in other tissues was shown in other studies in Fenneropenaeus chinensis, scophthalmus maximus and Paralichthys olivaceus (Li et al 2006;Sun, Liu, Qin, Zhang, Xing, Xu & Gao 2009;Wang, Ji, Li, Guo, Xing & Chang 2013). The differences can be explained by the different acetylation ratio of sulpha drugs in different species, for example, fish exhibits a higher acetylation capacity to sulpha drugs than crustaceans, and the reported species-specific acetylation ratios of sulpha drugs are 88%, 62.1%, 2% and 0% in human, Australian lepores album, Cyprinus carpio and Fenneropenaeus chinensis respectively (Grondel, Nouws & Haenen 1986;Vree, Hekster, Nouws & Baakman 1986;Yuan & Fung 1990;Zhang et al 2005). Samuelsen (2006) also reported that moderate concentrations of N-acetylated sulphadimethoxine were found in tissues and bile indicating N-acetylation to be a less important metabolic pathway for sulphadimethoxine in cod (Gadus morhua).…”

Section: Distribution Of Sm 2 In Tissues Of F Chinensismentioning

confidence: 99%

Environmental fate and pharmacokinetics of sulphamethazine inFenneropenaeus chinensisshrimp production systems after oral administration

Sun

Zhai

et al. 2015

Aquac Res

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The antimicrobial sulphamethazine is widely used in aquaculture for the prevention and treatment of bacterial diseases. Residues of sulphamethazine have been detected in aquatic environments and in edible tissues of aquaculture fish and shrimps at relatively low, but detectable concentrations. Detailed information on the environmental fate and pharmacokinetics of sulphamethazine in aquaculture species is essential to predict possible ecological risks and to provide recommendations on appropriate dosages and withdrawal periods. In this study we investigated the distribution of sulphamethazine in water and sediments of Fenneropenaeus chinensis shrimp ponds treated with 50, 100 and 150 mg kg−1·bw of sulphamethazine for 5 days and measured the uptake and elimination dynamics of sulphamethazine in different shrimp organs and tissues. Results of the HPLC analysis showed highest sulphamethazine concentrations in shrimp tissues, followed by sediments and water. The rank order of the mean concentrations of sulphamethazine in shrimp tissues and organs was hepatopancreas> plasma≈ stomach> muscle≈ gill≈ intestine> carapace. The results also demonstrated a significant dose‐dependent accumulation of sulphamethazine in the different biological and environmental compartments. Sulphamethazine decreased gradually with the time in all of the three compartments. The mean half‐life of sulphamethazine in sediment and water was 2.15 and 2.17 days respectively. A withdrawal period of 10 days or more is proposed for F. chinensis orally treated with sulphamethazine in order to meet the current food safety standards.

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Pharmacokinetics, Metabolism, and Renal Excretion of Sulfadimidine and Its N4-Acetyl and Hydroxy Metabolites in Humans

Cited by 18 publications

References 0 publications

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

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

Bioconcentration and Elimination of Sulfamethazine and Its Main Metabolite in Sturgeon (Acipenser schrenkii)

Environmental fate and pharmacokinetics of sulphamethazine inFenneropenaeus chinensisshrimp production systems after oral administration

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