Digoxin biotransformation

Gault, M. H.; Longerich, L; Loo, Jack C K; Ko, Patrick T H; Fine, Adrian; Vasdev, Sudesh; Dawe, Madonna

doi:10.1038/clpt.1984.11

Cited by 39 publications

(21 citation statements)

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“…The pa tient's renal dysfunction was also an important factor. Since it could not be eliminated to a significant degree in the urine or via hemodialysis [4], more digoxin became available for metabolism [14], A reduced volume of dis tribution for digoxin has been reported in renal failure [7] and could not be discounted as a contributing factor in this patient. Such displacement of digoxin from tissue stores, possibly by uremic toxins, would make more drug available for hepatic metabolism.…”

Section: Discussionmentioning

confidence: 99%

False-Positive Digoxin Measurements due to Conjugated Metabolite Accumulation in Combined Renal and Hepatic Dysfunction

Vlasses

Besarab²,

Lottes³

et al. 1987

Am J Nephrol

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A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration.

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Section: Discussionmentioning

confidence: 99%

False-Positive Digoxin Measurements due to Conjugated Metabolite Accumulation in Combined Renal and Hepatic Dysfunction

Vlasses

Besarab²,

Lottes³

et al. 1987

Am J Nephrol

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“…The same system was used to evaluate compounds in urine which were reactive with antibody to digoxin [6] except that the other half of each of the 200 eluted fractions was assayed for 'digoxin-like materials' using the standard digoxin RIA (Kallestad Labs), after evaporation of the solvent and reconstitution in digoxin-free serum. …”

Section: Methodsmentioning

confidence: 99%

“…At that time, the SDC was 4.2 ng/ml before dialysis (day 13). [6] Assay of serum collected on day 12, 5 h after adminis tration of 3H-digoxin-l2a at the end of dialysis when the serum digoxin by RIA was 3.0 ng/ml, showed the first two peaks which are polar metabolites, to be only 3 and 5% of the total radioactivity, respectively. Other metabo lites includingdigoxigenin and its mono-and bis-digitoxosides were all < 1% and the remaining 90% of the radio activity chromatographed as digoxin.…”

Section: Comparison O F Four Ria Kits For Digoxinmentioning

confidence: 99%

Rising Serum Digoxin without Further Dosage in Acute Renal Failure

Gault¹,

Gallway²,

Fine³

et al. 1984

Nephron

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A 73-year-old man was given a total of 1 mg of digoxin intravenously over 3 days, close to the time that he developed acute renal failure with oligo-anuria. He received no cardiac glycosides before or after this 3-day period. 2 days after the last dose, the serum digoxin concentration (SDC) was 2.9 ng/ml, yet a peak value of 4.2 ng/ml was reached only 11 days later. The SDC remained above 2 ng/ml for another week, until urine output began to increase appreciably. As renal function improved, the SDC gradually fell to become undetectable 32 days after the last dose. Values for apparent volume of distribution calculated from the total dose, and also determined after injection of tritiated digoxin, suggest that the rise in SDC in the absence of additional doses was due in large part to a decrease in the apparent volume of distribution. Dosage and parameters of toxicity should be carefully monitored in patients receiving digoxin who develop acute renal failure.

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confidence: 99%

“…Digoxin is known to be converted metabolically to digoxigenin bis-digitoxoside, digoxigenin mono-digitoxoside and digoxigenin by cleavage of the sugar moiety. 1,2) In addition, it is metabolized to dihydrodigoxin by reduction of the double bond in the lactone ring.3)The analysis of digoxin in biological fluids can be performed by immunoassays. The antisera used for these immunoassays are produced by immunization with a haptencarrier protein conjugate, which is coupled to the terminal digitoxose of digoxin using periodate oxidation.…”

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confidence: 99%

Development of Radioimmunoassay for Measurement of Serum Digoxin in Digitalized Patients Using Novel Anti-digoxin Antiserum.

Ikeda

Araki

Takimoto

et al. 2002

Biological & Pharmaceutical Bulletin

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Digoxin is the most widely used cardiac glycoside for the treatment of congestive heart failure and atrial fibrillation. Digoxin is known to be converted metabolically to digoxigenin bis-digitoxoside, digoxigenin mono-digitoxoside and digoxigenin by cleavage of the sugar moiety. 1,2) In addition, it is metabolized to dihydrodigoxin by reduction of the double bond in the lactone ring.3)The analysis of digoxin in biological fluids can be performed by immunoassays. The antisera used for these immunoassays are produced by immunization with a haptencarrier protein conjugate, which is coupled to the terminal digitoxose of digoxin using periodate oxidation. 4,5) These antisera show high cross-reactivity with metabolites formed by the successive cleavage of the digitoxose residues. [6][7][8] In the radioimmunoassay (RIA) for determining digoxin concentrations in serum, 3 H-and 125 I-labeled digoxin derivatives have been widely used. [8][9][10] We recently reported the preparation and antigenic properties of digoxin-bovine serum albumin (BSA) conjugates linked at the digitoxose C-3Ј and C-3Љ positions. 11,12) The properties of the antisera were characterized by RIA for [ 3 H]-digoxin. Although the antiserum elicited by digoxin 3Ј-hemisuccinate-BSA conjugate possesses high specificity for digoxin, it still lacks the sensitivity needed for measurement of digoxin concentrations in serum. The sensitivity of RIA increases using a tracer whose specific radioactivity is high. In the present study, we describe development of a type of RIA of digoxin 3Ј-hemisuccinyl-[ 3 H]leucine using the antiserum elicited by digoxin 3Ј-hemisuccinate-BSA conjugate for measuring digoxin in serum from digitalized patients, and compare its performance with commercially available anti-digoxin BSA serum and monoclonal anti-digoxin. , and Dextran T-70 from Pharmacia Fine Chemicals (Uppsala, Sweden). Norit SX and other general reagents were supplied by Wako Pure Chemical Industries (Osaka, Japan). Digoxigenin, and its mono-and bis-digitoxosides were prepared by hydrolysis of digoxin according to the methods of Kaiser and his colleagues. MATERIALS AND METHODS Materials 13)RIA was performed in phosphate saline buffer (pH 7.4) containing K 2 HPO 4 (0.696 g), NaH 2 PO 4 · H 2 O (0.138 g), NaCl (4.39 g), and BSA (1.0 g) in H 2 O (500 ml). A dextrancoated charcoal suspension was prepared by continuously stirring Norit SX (500 mg) and Dextran T-70 (50 mg) in cold phosphate saline buffer (40 ml) for 10 min prior to use.The antiserum (antibody (A)) was prepared by immunizing rabbit with digoxin 3Ј-hemisuccinate-BSA conjugate. 12)The commercial anti-digoxin BSA serum (antibody (B)) and monoclonal anti-digoxin (antibody (C)) were supplied by BioMakor Co. (Rehovot, Israel).Apparatus The melting point was determined with a Yanagimoto micro hot-stage apparatus and is uncorrected. Optical rotation was measured with a JASCO DIP-370 digital polarimeter. FAB-MS measurement was made on a JEOL HX-100 instrument equipped with a FAB ion source using glycerol and NaCl as th...

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Digoxin biotransformation

Cited by 39 publications

References 0 publications

False-Positive Digoxin Measurements due to Conjugated Metabolite Accumulation in Combined Renal and Hepatic Dysfunction

False-Positive Digoxin Measurements due to Conjugated Metabolite Accumulation in Combined Renal and Hepatic Dysfunction

Rising Serum Digoxin without Further Dosage in Acute Renal Failure

Development of Radioimmunoassay for Measurement of Serum Digoxin in Digitalized Patients Using Novel Anti-digoxin Antiserum.

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