Convallatoxin, the active cardiac glycoside of lily of the valley, minimally affects the ADVIA Centaur digoxin assay.

OBJECTIVE: Lily of the valley is a poisonous plant due to the presence of the cardiac glycoside convallatoxin which is known to interfere with serum digoxin measurement using the LOCI digoxin assay and other digoxin assays. We evaluated potential interference of convallatoxin as well as extract of lily of the valley with the ADVIA Centaur digoxin assay by comparing results obtained using the LOCI digoxin assay. MATERIALS AND METHODS: Aliquots of a drug-free serum pool and a digoxin serum pool were supplemented with nanograms to 1 µg quantities of convallatoxin or 1.0 and 2.5 µL of lily of the valley extract per milliliter of serum followed by measurement of digoxin concentrations using the LOCI and ADVIA Centaur digoxin assays. RESULTS: Apparent digoxin concentrations were minimal using the ADVIA Centaur digoxin assay when aliquots of drug-free serum were supplemented with convallatoxin or extract of lily of the valley but apparent digoxin levels were very high using the LOCI digoxin assay. Moreover, minimal interference in serum digoxin measurement using the ADVIA Centaur digoxin assay was observed when aliquots of serum digoxin pool were further supplemented with lily of the valley extract. As expected, the LOCI digoxin assay showed significant interference of convallatoxin in serum digoxin measurement. CONCLUSIONS: Significant interference of convallatoxin in serum digoxin measurement using the LOCI digoxin assay could be minimized using the ADVIA Centaur digoxin assay.

The iDigoxin Assay is More Sensitive than LOCI Digoxin Assay for Rapid Detection of Convallatoxin, the Active Cardiac Glycoside of Lily of The Valley.

OBJECTIVE: Lily of the valley is a poisonous plant due to the presence of the cardiac glycoside convallatoxin. We compared two immunoassays (LOCI digoxin assay and iDigoxin assay) for rapid detection of convallatoxin if present in human serum. MATERIALS AND METHODS: Aliquots of a drug free serum pool and a digoxin serum pool were supplemented with microliter amounts of lily of the valley extract or nanogram to microgram quantities of convallatoxin, followed by measurement of apparent digoxin concentrations using the LOCI and iDigxoin assays. RESULTS: Apparent digoxin concentrations were observed when aliquots of a drug free serum pool were supplemented with convallatoxin or lily of the valley extract using both assays but apparent digoxin concentrations were significantly higher using the iDigoxin assay. In addition, the interference of convallatoxin in serum digoxin measurement was also significantly higher using iDigxoin assay compared to the LOCI digoxin assay. CONCLUSIONS: The iDigxoin assay is more sensitive in detecting convallatoxin in human serum.

Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs.

Cardiac glycosides have been reported to exhibit cytotoxic activity against several different cancer types, but studies against colorectal cancer are lacking. In a screening procedure aimed at identifying natural products with activity against colon cancer, several cardiac glycosides were shown to be of interest, and five of these were further evaluated in different colorectal cancer cell lines and primary cells from patients. Convallatoxin (1), oleandrin (4), and proscillaridin A (5) were identified as the most potent compounds (submicromolar IC50 values), and digitoxin (2) and digoxin (3), which are used in cardiac disease, exhibited somewhat lower activity (IC50 values 0.27-4.1 microM). Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan). The combination of 2 and oxaliplatin exhibited synergism including the otherwise highly drug-resistant HT29 cell line. A ChemGPS-NP application comparing modes of action of anticancer drugs identified cardiac glycosides as a separate cluster. These findings demonstrate that such substances may exhibit significant activity against colorectal cancer cell lines, by mechanisms disparate from currently used anticancer drugs, but at concentrations generally considered not achievable in patient plasma.

Elimination of cardiac glycosides through hemofiltration.

Elimination of three different cardiac glycosides by hemofiltration was investigated using the flat bed RP-6 (Rhône-Poulenc, Paris). At a filtration rate of 59 +/- 9 ml/min the mean clearance of 3-H-g-strophanthin was 54.9 +/- 10.4, that of a 3-H-digoxin and unlabelled digoxin 36.7 +/- 6.6 and that of digitoxin 4.6 +/- 2.8 ml/min. It is concluded from these results that hemofiltration is able to eliminate more than 50% of the amount excreted during the same period of time by normal kidneys. Elimination of cardiac glycosides by continuous hemofiltration is high enough to justify its use in digitalis intoxication, particularly because of the excellent control of electrolyte balance with this new method of detoxification.