Vergleichende Untersuchungen über die Wirkung einiger Sulfone und Sulfonamide in vitro und vivo bei Streptokokken

Wagner, W. H.; Kimmig, J

doi:10.1007/bf01635612

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“…However, the sulphoxide has definite activity in vivo against these same organisms in the mouse and the guinea-pig. These findings have led to the suggestion that the sulphoxide is activated by conversion to the sulphone in the animal body (Jensen and Schmith, 1943;Youmans, Feldman, and Doub, 1946;Wagner and Kimmig, 1946).In order to evaluate the specific usefulness of the sulphoxide in leprosy it is desirable to know the extent of its conversion to dapsone in the human body. The metabolic fate of sulphoxides varies with different compounds and in different species.…”

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METABOLISM AND EXCRETION OF DI(p‐AMINOPHENYL) SULPHOXIDE IN DIFFERENT ANIMAL SPECIES

Levi

Snow

1960

British Journal of Pharmacology and Chemotherapy

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Rabbits, rats and guinea-pigs were treated with di(p-aminophenyl) sulphoxide and their urines exdmined by an analytical method which permits the simultaneous determination of this compound and of dapsone [di(p-aminophenyl) sulphone] which is a possible product of metabolic oxidation. The method gives for each drug the total of free compound plus acid-labile conjugates. All three species excreted unchanged drug together with dapsone. With rats and guinea-pigs about 33% of the excretion is dapsone, but with rabbits only 6 to 12%. The rate of combined excretion is much greater in rabbits than in the other two species. These results are discussed in relation to the significance of di(p-aminophenyl) sulphoxide as a drug in the treatment of leprosy.Di(p-aminophenyl) sulphoxide has received favourable preliminary reports in clinical trials against leprosy (Buu-Hoi, Khuyen, and Xuong, 1955;Davey, Kissaun, and Moneta, 1957;Laviron, Lauret, Kerbastard, and Jardin, 1957), and there has been a suggestion that its action might be in some ways different from that of dapsone, di(p-aminophenyl) sulphone. Various workers have shown the sulphoxide to be almost without action in vitro against micro-organisms including pneumococci, haemolytic streptococci, and Mycobacterium tuberculosis H37Rv, in contrast to the considerable activity of dapsone in these species. However, the sulphoxide has definite activity in vivo against these same organisms in the mouse and the guinea-pig. These findings have led to the suggestion that the sulphoxide is activated by conversion to the sulphone in the animal body (Jensen and Schmith, 1943;Youmans, Feldman, and Doub, 1946;Wagner and Kimmig, 1946).In order to evaluate the specific usefulness of the sulphoxide in leprosy it is desirable to know the extent of its conversion to dapsone in the human body. The metabolic fate of sulphoxides varies with different compounds and in different species. A number of instances are known where thioethers are oxidized to sulphoxides and are excreted in this form rather than as sulphones, for example, in the metabolism of phenothiazine (Whitten, Filmer, and Clare, 1947), chlorpromazine (Salzman andBrodie, 1956), and a pyrazolidinedione containing an alkylthio group (Burns, Yu, Ritterband, Perel, Gutman, and Brodie, 1957); the oxidation of di(p-aminophenyl) sulphide by a guinea-pig liver microsome preparation is said to go to the sulphoxide but no further (Gillette, Kamm, and Brodie, 1959). On the other hand, sulphides can be oxidized in vivo to the sulphone, for example, p-methylthioaniline (Rose and Spinks, 1948), and the catabolism of ethanethiol probably follows this route after methylation (Snow, 1957;Lowe, 1960 Francis and Spinks (1950) to be applied to both components.Procedure.-Urine samples (5 ml.) are acidified with N HC1 (2.5 ml.); they are left for 1 hr. at 20 to 250 to allow for hydrolysis of acid-labile conjugates. After neutralization with N NaOH (2.5 ml.) the samples are diluted to contain 3 to 40 fig. /ml. of either sulphoxide or sulphone. For es...

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confidence: 99%