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Amitava Dasgupta - One of the best experts on this subject based on the ideXlab platform.
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clinically insignificant negative interferences of spironolactone potassium canrenoate and their common metabolite canrenone in new dimension vista loci Digoxin immunoassay
Journal of Clinical Laboratory Analysis, 2012Co-Authors: Amitava Dasgupta, Myrtle Johnson, Tamal K SenguptaAbstract:Spironolactone, a potassium-sparing diuretic metabolized to canrenone is often used with Digoxin to treat various conditions including congestive heart failure. Potassium canrenoate is a similar drug, which is also metabolized to canrenone. Due to reported both positive and negative interference of spironolactone, potassium canrenoate, and their common metabolite canrenone with Digoxin immunoassays, we investigated potential interference of these compounds with the new homogenous sequential chemiluminescent assay for Digoxin based on the luminescent oxygen channeling technology (LOCI Digoxin) for application on the Dimension and Vista platform. When aliquots of a drug-free serum pool were supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone and apparent Digoxin values were measured using Dimension Vista LOCI Digoxin assay, we observed no detected value except when aliquots were supplemented with very high amounts of potassium canrenoate or canrenone. However, we observed that apparent Digoxin concentrations were very low. When aliquots of a serum Digoxin pool (prepared by pooling specimens from patients receiving Digoxin), were further supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone and serum Digoxin concentrations were remeasured using the LOCIDigoxin assay, only statistically significant falsely lower Digoxin values (negative interference) were observed in specimens containing very high amounts of canrenone or potassium canrenoate. However, such small bias may not have any clinical significance. We conclude that new Dimension Vista LOCI Digoxin assay is virtually free from interferences of spironolactone, potassium canrenoate, and their common metabolite canrenone.
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effect of spironolactone potassium canrenoate and their common metabolite canrenone on dimension vista Digoxin assay
Journal of Clinical Laboratory Analysis, 2010Co-Authors: Amitava Dasgupta, Myrtle JohnsonAbstract:Spironolactone, a potassium sparing diuretic metabolized to canrenone, is often used with Digoxin to treat various conditions including congestive heart failure. Potassium canrenoate is a similar drug that is also metabolized to canrenone. Due to reported interference of spironolactone, potassium canrenoate, and their common metabolite canrenone with Digoxin immunoassays, we investigated potential interference of these compounds with Dimension Vista Digoxin immunoassay using Flex reagent cartridge. Aliquots of a drug-free serum pool were supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone and apparent Digoxin values were measured using Dimension Vista Digoxin assay, we observed none-detected value except when aliquots were supplemented with higher amounts of spironolactone or canrenone. Similarly, when aliquots of a serum Digoxin pool (prepared by pooling specimens from patients receiving Digoxin) where further supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone, we observed moderately falsely elevated Digoxin values only in specimens containing higher amounts of spironolactone or canrenone. We conclude that spironolactone and canrenone but not potassium canrenoate may cause modest interference with Dimension Vista Digoxin assay but such interferences may not be clinically significant except with very high amounts of canrenone. J. Clin. Lab. Anal. 24:413–417, 2010. © 2010 Wiley-Liss, Inc.
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effect of spironolactone potassium canrenoate and their common metabolite canrenone on serum Digoxin measurement by Digoxin iii a new Digoxin immunoassay
Therapeutic Drug Monitoring, 2008Co-Authors: Amitava Dasgupta, Gertie Tso, Alice WellsAbstract:Abstract: Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with Digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with several Digoxin immunoassays at concentrations expected after therapeutic usage of these drugs and falsely elevate or lower serum Digoxin concentrations. Recently, Abbott Laboratories marketed a new Digoxin III immunoassay for application on the AxSYM analyzer. We studied the potential interference of these compounds with this new Digoxin assay. The Tina-quant assay was used as the reference method because spironolactone, potassium canrenoate, and canrenone do not interfere with serum Digoxin measurement using this assay. Aliquots of drug-free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin concentrations were measured using the Digoxin III assay and Tina-quant assay. Significant apparent Digoxin concentrations were observed when the Digoxin III Digoxin assay was used, but no apparent Digoxin levels was observed using the Tina-quant assay. When serum pools prepared from patients receiving Digoxin were further supplemented with these compounds in concentrations expected in sera of patients receiving these medications, falsely elevated Digoxin levels were observed using Digoxin III assay, but no statistically significant change was observed using the Tina-quant assay. We conclude that spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with the serum Digoxin measurements using the new Digoxin III assay.
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effect of asian ginseng siberian ginseng and indian ayurvedic medicine ashwagandha on serum Digoxin measurement by Digoxin iii a new Digoxin immunoassay
Journal of Clinical Laboratory Analysis, 2008Co-Authors: Amitava Dasgupta, Gertie Tso, Alice WellsAbstract:Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum Digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new Digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum Digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then Digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a Digoxin pool prepared from patients receiving Digoxin with various amounts of these herbal supplements and then measured Digoxin concentrations again using both Digoxin immunoassays. We observed modest apparent Digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent Digoxin in the range of 0.31-0.57 ng/ml), but no apparent Digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of Digoxin pool were further supplemented with these herbal supplements, Digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml Digoxin) increase in Digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml Digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free Digoxin does not eliminate the modest interferences of these herbal supplements in serum Digoxin measurement by the Digoxin III assay.
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Effect of Indian Ayurvedic medicine Ashwagandha on measurement of serum Digoxin and 11 commonly monitored drugs using immunoassays: study of protein binding and interaction with Digibind.
Archives of Pathology & Laboratory Medicine, 2007Co-Authors: Amitava Dasgupta, Amanda Peterson, Alice Wells, Jeffrey K ActorAbstract:● Context.—Ashwagandha, a popular Ayurvedic medicine, is now available in the United States. Alkaloids found in this herb have structural similarity with Digoxin. Objective.—To study potential interference of Ashwagandha with serum Digoxin measurement by immunoassays. Potential interference was also investigated with immunoassays for 11 other commonly monitored drugs. In addition, interaction of components of Ashwagandha with the Fab fragment of antiDigoxin antibody (Digibind) was investigated. Design.—Two different brands of liquid extract and 1 dry powdered form of Ashwagandha were used for this investigation. Aliquots of drug-free serum were supplemented with various concentrations of Ashwagandha and apparent Digoxin concentrations were measured by 3 Digoxin immunoassays. Mice were fed with Ashwagandha and apparent Digoxin concentrations were measured 1 and 3 hours after feeding. Potential interference of Ashwagandha with immunoassays of 11 other drugs was also investigated. Interaction of components of Ashwagandha with Digibind was studied in vitro. Results.—Significant apparent Digoxin concentrations were observed both in vitro and in vivo using the fluorescence polarization immunoassay of Digoxin, whereas the Beckman and the microparticle enzyme immunoassay Digoxin assay demonstrated minimal interference. Immunoassays of 11 other drugs tested were unaffected. When Ashwagandha extract was added to a serum pool containing Digoxin, falsely elevated Digoxin value was observed with fluorescence polarization immunoassay, but values were falsely lowered when measured by the microparticle enzyme immunoassay. Digibind neutralized Digoxin-like immunoreactive components of Ashwagandha in vitro. Conclusions.—Components of Ashwagandha interfered with serum Digoxin measurements using immunoassays. Digibind neutralized free Digoxin-like immunoreactive components of Ashwagandha. (Arch Pathol Lab Med. 2007;131:1298–1303)
Heba K Abdelhakim - One of the best experts on this subject based on the ideXlab platform.
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a novel source of the cardiac glycoside Digoxin from the endophytic fungus epicoccum nigrum isolation characterization production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation
Journal of Applied Microbiology, 2020Co-Authors: Elsayed R Elsayed, Ashraf S Ahmed, Heba K AbdelhakimAbstract:AIMS: Different endophytic fungi were isolated and screened for their Digoxin-producing ability. Strain improvement and different culture conditions were studied for more effective production of Digoxin. METHODS AND RESULTS: Among the isolated fungi, an isolate produced Digoxin in a concentration of 2.07 mg l(-1) . The Digoxin-producing fungal isolate was identified as Epicoccum nigrum Link according to the morphological features and phylogenetic analyses. The potentiality of the fungal strain for production enhancement of Digoxin was performed by gamma radiation mutagenesis. Gamma irradiation dose of 1000 Gy intensified the Digoxin yield by five-fold. Using this dose, a stable mutant strain with improved Digoxin productivity was isolated and the stability for Digoxin production was followed up across four successive generations. In the effort to increase Digoxin magnitude, selection of the proper cultivation medium, addition of some elicitors to the most proper medium and several physical fermentation conditions were tested. Fermentation process carried out in malt extract autolysate medium (pH 6.5) supplemented by methyl jasmonate and inoculated with 2 ml of 6-day-old culture and incubated at 25 degrees C for 10 days stimulated the highest production of Digoxin to attain 50.14 mg l(-1) . Moreover, cytotoxicity of Digoxin separated from the fungal culture was tested against five different cancer cell lines. Based on the MTT assay, Digoxin inhibited the proliferation of the five different cancer cell lines and the recorded 50% inhibitory concentration ranged from 10.76 to 35.14 mug ml(-1) . CONCLUSIONS: This is the first report on the production and enhancement of Digoxin using fungal fermentation as a new and alternate source with high productivity. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer new and alternate sources with excellent biotechnological potential for Digoxin production by fungal fermentation. Moreover, Digoxin proved to be a promising anticancer agent whose anticancer potential should be assessed in prospective cancer therapy.
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A novel source of the cardiac glycoside Digoxin from the endophytic fungus Epicoccum nigrum: isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation
Journal of applied microbiology, 2019Co-Authors: El-sayed R. El-sayed, Ashraf S Ahmed, Heba K AbdelhakimAbstract:Aims Different endophytic fungi were isolated and screened for their Digoxin-producing ability. Strain improvement and different culture conditions were studied for more effective production of Digoxin. Methods and results Among the isolated fungi, an isolate produced Digoxin in a concentration of 2·07 mg l-1 . The Digoxin-producing fungal isolate was identified as Epicoccum nigrum Link according to the morphological features and phylogenetic analyses. The potentiality of the fungal strain for production enhancement of Digoxin was performed by gamma radiation mutagenesis. Gamma irradiation dose of 1000 Gy intensified the Digoxin yield by five-fold. Using this dose, a stable mutant strain with improved Digoxin productivity was isolated and the stability for Digoxin production was followed up across four successive generations. In the effort to increase Digoxin magnitude, selection of the proper cultivation medium, addition of some elicitors to the most proper medium and several physical fermentation conditions were tested. Fermentation process carried out in malt extract autolysate medium (pH 6·5) supplemented by methyl jasmonate and inoculated with 2 ml of 6-day-old culture and incubated at 25°C for 10 days stimulated the highest production of Digoxin to attain 50·14 mg l-1 . Moreover, cytotoxicity of Digoxin separated from the fungal culture was tested against five different cancer cell lines. Based on the MTT assay, Digoxin inhibited the proliferation of the five different cancer cell lines and the recorded 50% inhibitory concentration ranged from 10·76 to 35·14 μg ml-1 . Conclusions This is the first report on the production and enhancement of Digoxin using fungal fermentation as a new and alternate source with high productivity. Significance and impact of the study These findings offer new and alternate sources with excellent biotechnological potential for Digoxin production by fungal fermentation. Moreover, Digoxin proved to be a promising anticancer agent whose anticancer potential should be assessed in prospective cancer therapy.
Pradip Datta - One of the best experts on this subject based on the ideXlab platform.
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a new enzyme linked chemiluminescent immunosorbent Digoxin assay is virtually free from interference of spironolactone potassium canrenoate and their common metabolite canrenone
Journal of Clinical Laboratory Analysis, 2006Co-Authors: Amitava Dasgupta, Edward Kang, Pradip DattaAbstract:Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are sometimes used in conjunction with Digoxin for patient management. Spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with serum Digoxin measurement using various immunoassays. Recently a new enzyme-linked chemiluminescent immunosorbent Digoxin assay (ECLIA-Digoxin) became commercially available for application on the ADVIA IMS 800i modular system (Bayer HealthCare, Tarrytown, NY). We investigated the potential interference of spironolactone and related compounds in this assay by comparing the results with the fluorescence polarization immunoassay (FPIA), which is known to have significant cross-reactivity with these compounds as well as a turbidimetric assay for Digoxin with no known cross-reactivity with spironolactone and related compounds. Aliquots of drug free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin concentrations were measured. No apparent Digoxin concentration was observed using the ECLIA-Digoxin or turbidimetric assay. When serum pools prepared from patients receiving Digoxin were further supplemented with these compounds, we observed no significant change in Digoxin concentrations in the presence of these compounds with the ECLIA-Digoxin. We conclude that this assay is virtually free from interferences from spironolactone, potassium canrenoate and their common metabolite canrenone. J. Clin. Lab. Anal. 20:204–208, 2006. © 2006 Wiley-Liss, Inc.
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interference of endogenous Digoxin like immunoreactive factors in serum Digoxin measurement is minimized in a new turbidimetric Digoxin immunoassay on advia 1650 analyzer
Therapeutic Drug Monitoring, 2004Co-Authors: Pradip Datta, Amitava DasguptaAbstract:Endogenous Digoxin-like immunoreactive factors (DLIF) cross-react with antiDigoxin antibody and falsely elevate or lower measured serum Digoxin concentrations, depending on the assay design. Recently, Bayer Diagnostics released a turbidimetric assay for Digoxin on the ADVIA 1650 analyzer. We studied potential interference of DLIF with this new Digoxin assay. We analyzed 40 serum specimens from patients who have pathologic conditions that may increase serum DLIF concentrations. These patients were never exposed to Digoxin or other agents that may lead to a measurable Digoxin concentration. We also analyzed five specimens from autopsy and five specimens from neonates. Apparent Digoxin concentrations were measured using the new turbidimetric Digoxin assay, the fluorescence polarization immunoassay (FPIA, Abbott Laboratories, Abbott Park, IL), and also the chemiluminescent immunoassay (CLIA, Bayer Diagnostics). We observed measurable apparent Digoxin levels with the FPIA in 5 uremic patients (range 0.24-0.86 ng/mL), 6 patients with liver disease (range 0.21-0.72 ng/mL), in 3 patients in the third trimester of pregnancy (0.21-26 ng/mL), and in 3 neonates (range 0.21-0.46 ng/mL). Four out of 5 autopsy specimens showed measurable apparent Digoxin concentrations (0.23-0.81 ng/mL). In contrast, only 1 specimen (a uremic patient) showed an apparent Digoxin concentration of 0.26 ng/mL with the turbidimetric Digoxin immunoassay (FPIA value 0.86 ng/mL, CLIA value 0.32 ng/mL). Because DLIF is absent in the protein-free ultrafiltrate, we also measured free Digoxin concentrations in DLIF-positive patients to ensure that the apparent Digoxin concentrations were caused by DLIF. We observed no apparent Digoxin concentrations in the protein-free ultrafiltrate in any DLIF-positive specimens. When serum specimens containing elevated concentrations of DLIF but no Digoxin were supplemented with a known concentration of Digoxin, we observed falsely elevated Digoxin concentrations by the FPIA, as expected. In contrast, we observed a good agreement between the target and observed concentrations when the new turbidimetric assay was used. We conclude that DLIF has minimal effect on serum Digoxin measurements by the new turbidimetric assay.
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a new turbidometric Digoxin immunoassay on the advia 1650 analyzer is free from interference by spironolactone potassium canrenoate and their common metabolite canrenone
Therapeutic Drug Monitoring, 2003Co-Authors: Pradip Datta, Amitava DasguptaAbstract:Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with Digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for Digoxin and falsely elevate measured serum Digoxin concentrations. Recently a new turbidometric assay for Digoxin became commercially available from Bayer Diagnostic for application on the ADVIA 1650 Chemistry analyzer. We studied the potential interference of these compounds in this new Digoxin assay. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin concentrations were measured. We observed apparent Digoxin concentrations with the FPIA Digoxin assay as expected but observed no apparent Digoxin levels with the new turbidometric immunoassay. When serum pools prepared from patients receiving Digoxin were supplemented with these compounds in concentrations expected in serum in patients receiving these medications, we observed falsely elevated Digoxin levels with the FPIA Digoxin assay, but no statistically significant change was observed with the new turbidometric assay. We conclude that the new turbidometric assay for Digoxin is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone.
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bidirectional positive negative interference of spironolactone canrenone and potassium canrenoate on serum Digoxin measurement elimination of interference by measuring free Digoxin or using a chemiluminescent assay for Digoxin
Journal of Clinical Laboratory Analysis, 2002Co-Authors: Amitava Dasgupta, Alice Wells, Helene Saffer, Pradip DattaAbstract:Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with Digoxin in clinical practice. Spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for Digoxin, and can falsely elevate serum Digoxin concentrations. Serum Digoxin concentrations were falsely lowered when the microparticle enzyme immunoassay (MEIA) was used. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin activities were measured. We observed Digoxin-like activities in the FPIA, but observed no activity with the MEIA or the chemiluminescent assay (CLIA). However, when serum Digoxin pools prepared from patients receiving Digoxin were supplemented with these compounds, we observed suppression of total Digoxin levels with the MEIA. In contrast, no interference was observed in the presence of these compounds when CLIA was used for Digoxin measurement. These compounds are strongly protein-bound, and no apparent Digoxin activity was observed in the protein-free ultrafiltrate when drug-free sera were spiked with high levels of these compounds. Taking advantage of strong protein binding of these compounds and weak protein binding of Digoxin (25%), interference of spironolactone, canrenone, and potassium canrenoate in FPIA and MEIA Digoxin assays can be mostly eliminated by monitoring free Digoxin concentration. Another approach to avoid this interference is to use the CLIA Digoxin assay. © 2002 Wiley-Liss, Inc.
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bidirectional positive negative interference in a Digoxin immunoassay importance of antibody specificity
Therapeutic Drug Monitoring, 1998Co-Authors: Pradip Datta, Amitava DasguptaAbstract:The importance of high specificity in immunoassays used in therapeutic monitoring is highlighted by a case study in which therapeutic-to-toxic borderline Digoxin levels were measured by a Digoxin immunoassay in the serum sample from a patient administered digitoxin rather than Digoxin. The sample, mistakenly sent to the laboratory for Digoxin analysis, gave discordant results in three Digoxin immunoassays: 1.99 and 0.79 ng/ml in assays using polyclonal antibodies (fluorescence-polarization immunoassay and microparticle enzyme immunoassay, respectively), and <0.1 ng/ml in a chemiluminescent immunoassay using more specific monoclonal antibody. The presence of digitoxin (approximately 40 ng/ml) in the sample was confirmed by three different digitoxin immunoassays. Based on these results, the interference of different levels of digitoxin was studied in the presence of 0, 0.85, 1.9, and 4.7 ng/ml Digoxin in all three Digoxin assays. The chemiluminescent assay showed no significant interference. The fluorescence-polarization immunoassay showed positive interference in all cases; however, the microparticle enzyme immunoassay showed a bidirectional interference: a positive interference observed at Digoxin level <1.8 ng/ml, changing to a negative interference at higher Digoxin concentrations. The authors conclude that in countries such as Germany, where both Digoxin and digitoxin may be prescribed, caution should be used to interpret Digoxin immunoassay results. Digoxin assays, with cross-reactivity to digitoxin <0.1% should be used.
Nicholas A. Buckley - One of the best experts on this subject based on the ideXlab platform.
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Clinical experience with titrating doses of Digoxin antibodies in acute Digoxin poisoning. (ATOM-6)
2021Co-Authors: Betty S. Chan, Geoffrey K. Isbister, Angela Chiew, Katherine Isoardi, Nicholas A. BuckleyAbstract:For acute Digoxin poisoning, it has been recommended to give bolus doses of 10–20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of Digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity. This is a prospective observational study of patients with acute Digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of Digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum Digoxin concentrations. Outcomes were recorded and analysed. From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5–25). Median heart rate (HR) was 41 beats/min before treatment. Initial median Digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9–20) [11.2 µg/L(IQR: 8.4–15.4)] and 5 mmol/L (IQR: 4.5–5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5–20 vials. Twenty-one patients received repeated titrated doses (1–2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2–7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of Digoxin ingested or measured serum concentration, respectively. Twelve had free Digoxin concentrations measured. Free Digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of Digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute Digoxin toxicity. The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute Digoxin poisoning.
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physiologically based pharmacokinetic modelling of acute Digoxin toxicity and the effect of Digoxin specific antibody fragments
Clinical Toxicology, 2019Co-Authors: Lucy M. Bracken, Betty S. Chan, Nicholas A. BuckleyAbstract:Context: Recommended doses of Digoxin-specific antibody fragments (Digoxin-Fab) for treatment of acute Digoxin poisoning are pharmacokinetically unsubstantiated and theoretically excessive. Physiol...
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Physiologically based pharmacokinetic modelling of acute Digoxin toxicity and the effect of Digoxin-specific antibody fragments
2019Co-Authors: Lucy M. Bracken, Betty S. Chan, Nicholas A. BuckleyAbstract:Context: Recommended doses of Digoxin-specific antibody fragments (Digoxin-Fab) for treatment of acute Digoxin poisoning are pharmacokinetically unsubstantiated and theoretically excessive. Physiologically based pharmacokinetic (PBPK) modelling creates clinical simulations which are closely related to physiological and pharmacokinetic behaviour. This paper details the formulation of a PBPK model of Digoxin and explores its use as a simulation tool for acute Digoxin toxicity and its management. Materials and methods: A PBPK model of Digoxin was constructed and validated for acute Digoxin poisoning management by comparing simulations with observed individual acute overdose patients. These simulations were compared with standard two-compartment PK model simulations. Results: PBPK model simulations showed good agreement with post-absorption plasma concentrations of Digoxin measured in 6 acute overdose patients. PBPK predictions were accurate to 1.5-fold or less of observed clinical values, proving to be more accurate than two-compartment simulations of the same patients which produced up to a 4.9-fold change. Conclusions: Compared to conventional two-compartment modelling, PBPK modelling is superior in generating realistic simulations of acute Digoxin toxicity and the response to Digoxin-Fab. Simulation capacity provides realistic, continuous data which has the potential to substantiate alternative, less expensive, and safer Digoxin-Fab dosing strategies for the treatment of acute Digoxin toxicity.
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Digoxin specific antibody fragments in the treatment of Digoxin toxicity
Clinical Toxicology, 2014Co-Authors: Betty S. Chan, Nicholas A. BuckleyAbstract:AbstractContext. Digoxin-specific antibody fragments (Digoxin-Fab) are widely regarded as a safe and effective treatment for the management of acute and chronic Digoxin poisoning. Calculated equimolar doses of Digoxin-Fab are high, very expensive, and infrequently used. Objective. To review the pharmacology, efficacy, effectiveness, indications, safety and the dosage of Digoxin-specific antibody fragments. Methods. Pubmed, Embase, Medline and Cochrane were searched from 1946 to May 2013 using the terms Digoxin, Digoxin-specific Fab, and Digoxin antibody. Pharmacology and kinetics of Digoxin and Digoxin-Fab. Digoxin acts via inhibition of Na+/K+ ATPase. It has a narrow therapeutic index. Digoxin has 60–80% bioavailability, a mean plasma half-life of 40 h and a volume of distribution (Vd) of 5–10 L/kg and low protein binding (20%). A 40-mg vial of Digoxin-Fab (DigiFab) binds 0.5 mg Digoxin. Digoxin-Fab has a mean plasma half-life of 19–30 h and a Vd of 0.4 L/kg. The half-lives of both Digoxin and Digoxin-Fa...
Alice Wells - One of the best experts on this subject based on the ideXlab platform.
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effect of spironolactone potassium canrenoate and their common metabolite canrenone on serum Digoxin measurement by Digoxin iii a new Digoxin immunoassay
Therapeutic Drug Monitoring, 2008Co-Authors: Amitava Dasgupta, Gertie Tso, Alice WellsAbstract:Abstract: Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with Digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with several Digoxin immunoassays at concentrations expected after therapeutic usage of these drugs and falsely elevate or lower serum Digoxin concentrations. Recently, Abbott Laboratories marketed a new Digoxin III immunoassay for application on the AxSYM analyzer. We studied the potential interference of these compounds with this new Digoxin assay. The Tina-quant assay was used as the reference method because spironolactone, potassium canrenoate, and canrenone do not interfere with serum Digoxin measurement using this assay. Aliquots of drug-free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin concentrations were measured using the Digoxin III assay and Tina-quant assay. Significant apparent Digoxin concentrations were observed when the Digoxin III Digoxin assay was used, but no apparent Digoxin levels was observed using the Tina-quant assay. When serum pools prepared from patients receiving Digoxin were further supplemented with these compounds in concentrations expected in sera of patients receiving these medications, falsely elevated Digoxin levels were observed using Digoxin III assay, but no statistically significant change was observed using the Tina-quant assay. We conclude that spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with the serum Digoxin measurements using the new Digoxin III assay.
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effect of asian ginseng siberian ginseng and indian ayurvedic medicine ashwagandha on serum Digoxin measurement by Digoxin iii a new Digoxin immunoassay
Journal of Clinical Laboratory Analysis, 2008Co-Authors: Amitava Dasgupta, Gertie Tso, Alice WellsAbstract:Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum Digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new Digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum Digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then Digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a Digoxin pool prepared from patients receiving Digoxin with various amounts of these herbal supplements and then measured Digoxin concentrations again using both Digoxin immunoassays. We observed modest apparent Digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent Digoxin in the range of 0.31-0.57 ng/ml), but no apparent Digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of Digoxin pool were further supplemented with these herbal supplements, Digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml Digoxin) increase in Digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml Digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free Digoxin does not eliminate the modest interferences of these herbal supplements in serum Digoxin measurement by the Digoxin III assay.
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Effect of Indian Ayurvedic medicine Ashwagandha on measurement of serum Digoxin and 11 commonly monitored drugs using immunoassays: study of protein binding and interaction with Digibind.
Archives of Pathology & Laboratory Medicine, 2007Co-Authors: Amitava Dasgupta, Amanda Peterson, Alice Wells, Jeffrey K ActorAbstract:● Context.—Ashwagandha, a popular Ayurvedic medicine, is now available in the United States. Alkaloids found in this herb have structural similarity with Digoxin. Objective.—To study potential interference of Ashwagandha with serum Digoxin measurement by immunoassays. Potential interference was also investigated with immunoassays for 11 other commonly monitored drugs. In addition, interaction of components of Ashwagandha with the Fab fragment of antiDigoxin antibody (Digibind) was investigated. Design.—Two different brands of liquid extract and 1 dry powdered form of Ashwagandha were used for this investigation. Aliquots of drug-free serum were supplemented with various concentrations of Ashwagandha and apparent Digoxin concentrations were measured by 3 Digoxin immunoassays. Mice were fed with Ashwagandha and apparent Digoxin concentrations were measured 1 and 3 hours after feeding. Potential interference of Ashwagandha with immunoassays of 11 other drugs was also investigated. Interaction of components of Ashwagandha with Digibind was studied in vitro. Results.—Significant apparent Digoxin concentrations were observed both in vitro and in vivo using the fluorescence polarization immunoassay of Digoxin, whereas the Beckman and the microparticle enzyme immunoassay Digoxin assay demonstrated minimal interference. Immunoassays of 11 other drugs tested were unaffected. When Ashwagandha extract was added to a serum pool containing Digoxin, falsely elevated Digoxin value was observed with fluorescence polarization immunoassay, but values were falsely lowered when measured by the microparticle enzyme immunoassay. Digibind neutralized Digoxin-like immunoreactive components of Ashwagandha in vitro. Conclusions.—Components of Ashwagandha interfered with serum Digoxin measurements using immunoassays. Digibind neutralized free Digoxin-like immunoreactive components of Ashwagandha. (Arch Pathol Lab Med. 2007;131:1298–1303)
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bidirectional positive negative interference of spironolactone canrenone and potassium canrenoate on serum Digoxin measurement elimination of interference by measuring free Digoxin or using a chemiluminescent assay for Digoxin
Journal of Clinical Laboratory Analysis, 2002Co-Authors: Amitava Dasgupta, Alice Wells, Helene Saffer, Pradip DattaAbstract:Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with Digoxin in clinical practice. Spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for Digoxin, and can falsely elevate serum Digoxin concentrations. Serum Digoxin concentrations were falsely lowered when the microparticle enzyme immunoassay (MEIA) was used. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent Digoxin activities were measured. We observed Digoxin-like activities in the FPIA, but observed no activity with the MEIA or the chemiluminescent assay (CLIA). However, when serum Digoxin pools prepared from patients receiving Digoxin were supplemented with these compounds, we observed suppression of total Digoxin levels with the MEIA. In contrast, no interference was observed in the presence of these compounds when CLIA was used for Digoxin measurement. These compounds are strongly protein-bound, and no apparent Digoxin activity was observed in the protein-free ultrafiltrate when drug-free sera were spiked with high levels of these compounds. Taking advantage of strong protein binding of these compounds and weak protein binding of Digoxin (25%), interference of spironolactone, canrenone, and potassium canrenoate in FPIA and MEIA Digoxin assays can be mostly eliminated by monitoring free Digoxin concentration. Another approach to avoid this interference is to use the CLIA Digoxin assay. © 2002 Wiley-Liss, Inc.
