Serum disappearance and urinary excretion of sulfamethoxypyridazine in goats.

Pharmacokinetics and urinary excretion of sulfamethoxypyridazine were determined in goats following single intravenous administration (100 mg/kg body weight). The disposition kinetics of sulfamethoxypyridazine could be best described by a 2-compartment open model. The distribution and elimination half life of the drug were 0.10 +/- 0.03 and 6.28 +/- 0.44 h, respectively. The values of apparent volume of distribution at steady state and total body clearance were found to be 0.39 +/- 0.02 l/kg and 0.73 +/- 0.06 ml/kg/min, respectively. The degree of acetylation was low as it ranged between 4.49 +/- 1.96 to 25.07 +/- 6.31% of the total drug in serum with an overall mean of 11.99 +/- 1.66%. Cumulative urinary excretion of sulfamethoxypyridazine was very low as only 2.97 +/- 0.50% of the total administered dose was excreted in urine during 24 h. The dosage regimen in goats would be 37.00 and 27.15 mg/kg body weight as the priming and maintenance doses respectively, to be repeated at 12 h intervals by intravenous route to achieve the bacteriostatic level of > or = 25 micrograms/ml.

[Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]. / Renale Ausscheidung von Langzeitsulfonamiden bei Flüssigkeitsbelastung und Anderung des pH-Wertes des Harns

The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.

Different inhibitory effects of 2,4-dinitrophenol, iodoacetate, and probenecid on renal excretion of p-aminohippurate, cyclopenthiazide, and sulfamethoxypyridazine in rats.

The present study was undertaken to determine whether the renal excretion of drugs can be modified by inhibition of the carrier system for organic acids in vivo. The renal excretion of p-aminohippurate is not influenced by 2,4-dinitrophenol but is reduced by iodoacetate and probenecid. The renal excretion of cyclopenthiazide is decreased by all inhibitors. Rats excrete only a very small portion of the administered dose of sulfamethoxypyridazine. Renal sulfamethoxypyridazine excretion is 3 times higher when the tubular reabsorption is blocked by simultaneous administration of NaHCO3. However, even then only a small portion of the injected dose is excreted. Renal sulfamethoxypyridazine excretion is only reduced by probenecid. This finding can be explained by the reduction of the urine volume. It can be concluded that p-aminohippurate and cyclopenthiazide are renally excreted by tubular secretion, whereas sulfamethoxy-pyridazine is excreted by glomerular filtration.

Disc-agar diffusion microbiological assay procedure for determining serum and urine levels of sulfacytine and other sulfonamides.

A reasonably precise, reproducible, and sensitive microbiological procedure for directly assaying sulfacytine and other sulfonamides as antibacterially active drugs has been developed by appropriately modifying the standard disc-agar diffusion technique. Blood and urine levels as low as 3 mug/ml may be determined through the use of a strain of Escherichia coli and a chemically defined agar medium devoid of sulfonamide antagonists. Results indicate that this assay method should be a useful adjunct to the Bratton-Marshall colorimetric procedure, by permitting the direct measurement of antibacterially active drug in clinical specimens.