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.

[Characteristics of the distribution of long-acting sulfanilamides in purulent pyelonephritis in rats]. / Osobennosti raspredeleniia dlitel'no deistvuiushchikh sul'fanilamidov pri sinegnoinom pielonefrite u krys.

Distribution of sulfalen, sulfadimethoxine and sulfamethoxypyridazine in the blood and organs of rats and binding of the drugs to the blood serum proteins of the animals with experimental P. aeruginosa pyelonephritis were studied. It was shown that in rats with P. aeruginosa pyelonephritis the levels of long-acting sulfanilamides in the blood and organs were lower, while the levels of their penetration through the histohematic barriers were higher, which was partially due to the decreased binding of sulfanilamides to blood proteins.

Biological availability of sulfamethoxypyridazine and sulfisomidine polymers.

Dissolution rates and apparent solubilities of forms I, II and III of Sulfamethoxypyridazine (1) and forms I and II of sulfisomidine (2) were determined in water at 37 degrees C. The ratios of apparent solubilities of I:II:III for 1 forms and I:II for 2 forms were 1:1.18:1.25 and 1:1.32 respectively. Upon long contact of 2 with water the ratio of II:I decreased. This has been attributed to gradual transformation of 2 from form II to I. Gastrointestinal absorption of form III of 1, in human volunteers, was studied in comparison with the more stable form I. The same study was carried out on forms I and II of 2. Data were correlated and expressed in availability rate constants (K1), applying the one compartment open: model. This and other parameters show that form III of 1 is 1.4 times as much absorbed as form I, and that the availability of the metastable form II of 2 is 1.2 times as much absorbed as the stable form I.

The influence of increasing albumin concentrations on the determination of the binding of sulfamethoxy-pyridazine to human and bovine serum albumin.

The binding of sulfamethoxypyridazine to human and bovine serum albumin was determined at eight constant molar drug/albumin ratios for seven different albumin concentrations ranging from 0.1% to 1.5%. The serum albumin concentration affects the determination of the albumin binding of the drug in two different ways. 1. The relative affinity of the albumins for the drug increases with increasing albumin concentrations, while the numbers of binding sites remain constant. 2. The association constants taken from Scatchard plots decrease with increasing albumin concentrations. It is concluded that a direct comparison of binding constants obtained with different albumin concentrations, as widely done, can lead to misinterpretations and should be avoided.

[Sensitivity to dapsone, sulfamethoxypyridazine and ethionamide of mycobacterium leprae taken from patients treated by the drugs]. / Sensibilité envers la dapsone, la sulfamethoxypyridazine et l'éthionamide, de Mycobacterium leprae provenant de malades traités par ces substances

Suspensions of M. leprae from skin biopsies of patients treated with dapsone (DDS) (four cases), sulfamethoxypyridazine (SMP) (six cases), and ethionamide (ETH) (seven cases), were inoculated into mouse foot pads and their sensitivity for the different drugs determined. Two strains were DDS resistant. Resistance appeared after 13 and 14 years respectively after the start of treatment. Five strains were isolated from patients treated with SMP. Relapses during sulfonamide treatment are considered to be due to the low effective serum concentrations reached by SMP, a situation which is aggravated by irregularities in drug intake. Fortunately all strains were sensitive to SMP and DDS as well. Four strains were ETH resistant. ETH resistance at the present moment reaches 4% and appeared in two cases six years after the start of treatment. It is concluded that SMP is not indicated for the treatment of multibacillary leprosy and that ETH can be used only in association with other drugs during the introductory phase of treatment of multibacillary forms of leprosy.

Drug-induced change in the distribution of sulfonamides in the mother rat and its fetus.

The distribution of a highly bound antibacterial sulfonamide was markedly altered in both the mother rat and its fetus by interfering with the binding of this drug to plasma protein in the mother. This effect was due to binding displacement, since the displacing agent had little or no effect on the distribution of another sulfonamide with very low binding to plasma protein.

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.