[Partition coefficients and Rm-values of cardenolides (author's transl)]. / Verteilungskoeffizienten und Rm-Werte von Cardenoliden.

Partition coefficients (P) of 48 cardenolides were determined in octanol/water. Furthermore Rm-values of most of these substances were measured in different thin-layer chromatography systems (TLC) and related to P. Regression analysis revealed that the best linear fit of the data was obtained when Rm-values from reversed-phase TLC on octanol impregnated silica-gel layer as stationary phase and methanol/water as mobile phase were correlated with log P (r = 0.91). A better correlation between these two sets of data was obtained by restricting the calculations to groups of cardenolides with similar structural features (r = 0.96-0.98). The present results are showing that Rm-values from reversed-phase TLC--a rapid and reproducible method with many advantages over the tedious measurement of P--can be used to predict P.

[Lipophilicity and enteral absorption of cardenolides (author's transl)]. / Lipophilie und enterale Resorption bei Cardenoliden.

Intestinal absorption of 15 cardenolides has been examined in cats. The 3H-labelled substances were injected intraluminally into ligated duodenal loops of anaesthetized animals. 3H-Concentrations were followed in the portal circulation and in the bile. 1 h after drug administration the duodenal sac was removed, and the residual in the lumen then was washed out and assayed radiochemically. The decrease of radioactivity during 1 h was calculated as extent of absorption (QR). Cardenolide absorption was compared with the corresponding in vitro parameters of lipophilicity like octanol/water partition coefficients and Rm values from reversed phase thin-layer chromatography. The Spearman rank sum correlation test revealed coefficients of 0.95 to 0.97. The result lends support to the use of the easily available Rm values as a good tool to predict intestinal absorption of various cardenolides.

[Lipophilicity-protein binding relationship in cardenolides (author's transl)]. / Lipophilie und Proteinbindung bei Cardenoliden.

By equilibrium dialysis the binding of 19 cardenolides and cardenolide conjugates to human plasma proteins has been measured. The binding constants were compared with octanol-water partition coefficients described previously. No correlation was found between the two properties. Glycosides and conjugates of a certain genine show the same extent of protein binding, even if some of the derivatives differ in their physicochemical properties more than by three log units. It is concluded that cardenolide protein binding depends solely on hydrophobic property of the genine involved.

[Studies on Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide). Part 1: Physico-chemical and chemical properties (author's transl)]. / Untersuchungen mit Xipamid (4-Chlor-5-sulfamoyl-2',6'-salicyloxylidid). Teil I: Physikalisch-chemische und chemische Eigenschaften.

The saluretic agent xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide; Aquaphor) is a lipophilic substance as demonstrated by solubilities and partition coefficients. In the physiological pH-range, however, xipamide forms an anion which has an octanol-water partition coefficient of approx. 1. Two steps of ionization were investigated photometrically. The first one gives rise to a phenolate anion; pKa1 = 4.75. In the second one, ionization of the sulfamoyl group occurs; pKa2 = 10. Xipamide is stable in acidic as well as in basic media at room temperature. But when xipamide is acted upon by strong alkali and elevated temperature, 2,6-xylidine is formed by hydrolysis. For analytic use UV-photometric, colorimetric and TLC data of xipamide are given.

[The saluretic effect of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylilide) in normal subjects]. / Die saluretische Wirkung von Xipamid (4-Chlor-5-sulfamoyl-2',6'-salicyloxylidid) bei gesunden Probanden

The diuretic and saluretic effectiveness of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor) is determined and compared to those of chlortalidone and furosemid in normal subjects. The substance is revealed as a potent diuretic agent. In the range of 0.035--0.750 mg/kg body weight the dose-response curve of orally administered xipamide for the increase of excretion of urine, sodium and potassium ion and chloride during 24 h is described. Observing the renal activity over a period of 3 days after a single administration the duration of action is found to be up to 24 h with its maximum within the first 12 h. In the following 2 days the degree of the physiological rebound effect depends on the preceding saluretic effect and thus on the given dose. The pattern of ion-excretion (Na

[Inhibition of carbonic anhydrase by xipamide (4-chloro-sulfamoyl-2',6'-salicyloxylidide) in the modified Philpot test]. / Die Hemmung der Carboanhydrase durch Xipamid (4-Chlor-5-sulfamoyl-2',6'-salicyloxylidid) im modifizierten Philpot-Test

The inhibition of carbonic anhydrase by xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor), a poorly watersoluble saluretic agent, is determined with the Philpot method in the presence of 5 per cent N,N-dimethyl-formamide. The addition of the amide does not affect the enzyme. For xipamide 1.1 times 10-5 M is found as the 50 per cent inhibitory concentration.