Sulfadimidine

This sequence is equally applicable to keto esters. Thus, condensation of guanidine with ethyl acetoacetate gives the pyrimidone, 134. Elaboration as above gives the pyrimidine, IJ5 acylation with the sulfonyl chloride (88) followed by hydrolysis yields sulfamerazine (107). Reaction of guanidine with beta dicarbonyl compounds gives the pyrimidine directly. Condensation of the base with acetonyl acetone affords the starting amine for sulfadimidine (108). ... 

Common Name Sulfamezathine, sulfadimerazine, sulfamidine, sulfadimethylpyrimidine, sulfadimidine (U.K. Name)... 

Sulfadimidine [5-68-1] Milk, tissues (M, K, L) PAb Plate Varied, depend 89... 

Franek et al developed an immunoassay for sulfadimidine, but they found that milk samples required dilution (1 100), and tissues required dilutions of 1 200 to 1 4000. The LOD was 0.02 pg kg from the buffer calibration curve with the IC50 at 0.15 pgkg The assay measured levels in milk from 10 to 100 pgkg with satisfactory precision. In swine muscle, kidney, and liver samples, levels from 20 to 500 pg kg could be measured when 2 g of tissue were homogenized with 20 mL of buffer and then diluted 1 20. 

Sulfamethazine/ Sulfadimidine H2N-< >-S02NH— Veterinary medicine Aquaculture Human medicine - High concentrations in landfill leaches in Denmark [4,5] - US streams 0.22 pg L-1 [20] - GW in Germany 10-100 pg L-1 [21] Non degradable in sewage treatment... 

Pharmacokinetics and Residues of Sulfadimidine and Its Acetyl and Hydroxy Metabolites in Food-Producing Animals... 

Recently the hydroxy metabolites of various sulfonamides could be Isolated and purified, so that specific HPLC techniques could be developed (22,23). As shown in Figure 1, sulfadimidine can be metabolized by hydroxylation at the 5 and 6 position of the pyrimidine ring and by the acetylation- deacetylation pathway (21). After hydroxylation, the metabolites may become glucuronidated and also acetylated (Figure 2). The hydroxy metabolites are microbiologically active and they can be potentiated by trimethoprim (13). 

Sodium sulfadimidine (33.3%) was obtained from A.U.V. (Cuyk,The Netherlands). N -acetylsulfadimidine (N -SDM), 6 -hydroxymethyl-sulfadimidine (SCH2OH) and 5-hydroxysulfadimidlne (SOH) were synthesized and isolated according Vree et al. (22,23). 

Figure 1. Molecular structures of sulfadimidine (SDM), its 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), its 6-hydroxymethyl-4-...

Table I summarizes the percentages of sulfadimidine and its metabolites in the plasma of the different species Table II shows the tissue to plasma drug concentration ratios for SDM and its metabolites, while Table III presents the urinary recovery data (for poultry urinary plus faecal recovery). The metabolic pathways observed in various species are summarized in a scheme (Figure 2). Selected data obtained are illustrated in Figures 3-9.

In the horse, hydroxylation is more important than acetylation as a metabolic pathway, with hydroxylation at the 5 position being dominant over hydroxylation of the 6-methyl group. Low percentages of metabolites are present in plasma, for N -SDM, 0.6 to 0.9 % for SCH2OH, 0.38 to 0.71 % and for SOH, 0.38 to 6.7 %. The plasma concentration-time curves of the metabolites run parallel to that of SDM. The elimination half-life of sulfadimidine varies between 5 and 14 h. The main metabolite in urine, accounting for 50 % of the drugs present (Table III), is the SOH and its glucuronide. 

Table II GONCENTRATIQN RATIO S OF SULFADIMIDINE AND ITS METABOLITES BETWEEN TISSUE SPECIMEN AND PLASMA.

Table III PLASMA ELIMINATION HALF-LIFE, AND URINARY RECOVERY OF SULFADIMIDINE AND ITS METABOLITES EXPRESSED AS PERCENTAGES OF THE DOSE ADMINISTERED (mean values) IN DIFFERENT SPECIES.

Figure 3. Plasma concentration-time curves of sulfadimidine (SDM), and its 6-methylhydroxy (CHoOH), 5-hydroxy (SOH) and its glucuronide (SOH N -acetyl CN ) and unknown (X) metabolites in a cow after an intravenous dose of 200 mg/kg sulfadimidine.

Figure 4. Disposition of sulfadimidine (SDM), its 6-methylhydro-xy (CH OH), 5-hydroxy (SOH) and N -acetyl (N ) metabolites in milk of a dairy cow following intravenous administration of 200 mg SDM/kg.

Figure 5. Disposition of sulfadimidine in urine, bile, plasma and tissues of calves following intravenous administration of 65 mg/kg intravenously.

Figure 9. Drug depletion time curves of sulfadimidine (SDM), and its metabolites (N, CH2OH) in the egg albumen and egg yolk during and after cessation of the administration of 100 mg SDM/kg during 5 days.

Laying-hens eliminate sulfadimidine rapidly by metabolic pathways including hydroxylation and acetylation. Following intravenous SDM administration, a biphasic elimination-time curve was noticed 10.2 + 3.3 H). Figure 8 shows the plasma disposition of SDM and its metabolites following an oral SDM bolus administration once daily of 100 mg/kg to a chicken. The percentage of N -SDM in plasma is the highest (Table I). Within 3 days of termination of the SDM therapy, plasma concentrations of SDM and its metabolites falls rapidly below the detection limit of the HPLC method (0.02 /ig/ml). 

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