Sulfadimidine metabolic pathways

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. 

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). 

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). 

The treatment of choice for coccidiosis is the sulfonamide antimicrobial agents (see Ch. 2). The sulfonamides disrupt folic acid and nicotinamide metabolism and coenzymes I and II by competing with para-aminobenzoic acid (PABA). Coccidia must manufacture their own folic acid and, therefore, this step is mandatory in the pyrimidine pathway of these parasites. Sulfamethazine (sulfadimidine) at 220mg/kg i.v. or orally, or sul-fadimethoxine (55mg/kg) orally or sulfathiazole (66mg/kg) orally, all once daily for 5-7 days, are used commonly for the treatment of equine coccidiosis. The signs of toxicity of the sulfonamides are covered extensively in Chapter 2. Crystalluria,... 

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