Absorption, metabolism and elimination of strophanthus glycosides in man

Abstract

In 33 healthy male volunteers, given a single oral and intravenous dose of cymarin (k-strophanthin-alpha), k-strophanthoside (k-strophanthin-gamma) and ouabain (g-strophanthin), enteral absorption and renal excretion of these glycosides and their metabolites were investigated by radioimmunoassay and HPLC. Cymarin was absorbed at 47% of the given dose. After intravenous injection 46% and after oral administration 21% of the given dose, i.e. the total amount as detected by radioimmunoassay which consisted of the unchanged glycoside and its metabolites, were excreted by the kidneys mainly as conjugated metabolites. The half-life of elimination, calculated from the total excreted amount was 13 h (i.v.) and 23 h (p.o.), respectively. k-Strophanthoside was absorbed at 16% of the given dose. After i.v.-injection 73% of the given dose was excreted by the kidneys with a half-life of elimination of 99 h. From this total amount about 70% was excreted as the unchanged drug, the remaining 30% as various metabolites. After oral administration 11% of the given dose were excreted with a half-life of elimination of 22 h. 80% of this amount consisted mainly of conjugated k-strophanthoside and conjugated metabolites as k-strophanthin-beta, cymarin, k-strophanthidin, cymarol and k-strophanthidol. Only 6% was excreted as the unchanged drug. Ouabain was absorbed after oral administration to a minimum of 1.4%. Given intravenously a total renal excretion of 33% of the given dose with a half-life of elimination of 23 h was measured. Of this 80% was unchanged ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt intake and depletion increase circulating levels of endogenous ouabain in normal men

“…5). The slope of the relationship shows that the urinary clearance is an important determinant of the circulating EO, and this interpretation is consistent also with elevated EO in patients with chronic renal failure (46) and with the key role of the kidney in the disposition of intravenous ouabain (47,51). However, although the urinary excretion of EO is significant, the present studies reveal also that the bulk of the filtered load of EO is likely subject to extensive renal reabsorption.…”

Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

“…The names of drug and drug‐like compounds and related data are listed in Table 1 and 2. The absorption data was collected and evaluated from 244 papers 1–5, 8–12, 18–251. The following information concerning human drug absorption was recorded from the literature: absorption data given from the literature;oral bioavailability or absolute bioavailability;percentage of cumulative urinary excretion of unchanged drug and its metabolites following oral and intravenous administration;percentage of metabolites in urine or first‐pass effect following oral and intravenous administration;percentage of unchanged drug in urine following oral and intravenous administration;percentage of excretion of drug in bile following oral and intravenous administration;percentage of cumulative excretion of drug in feces following oral and intravenous administration;total recovery of drug in urine and feces following oral and intravenous administration;single dose level in mg or mg/kg and daily oral dose in mg. …”

Discovery of Novel Antifungal (1,3)-β- d -Glucan Synthase Inhibitors

“…In addition to the in vitro antifungal activity, two of the compounds, ascosteroside and enfumafungin, have detectable activity against C. albicans in animal models (18; Pelaez, submitted). It is interesting that the oral absorption properties of some terpenoid glycosides have been characterized by others (10,51). One of these agents, digoxin, is therapeutically effective through an oral route of administration.…”