Methodological Causes of Discrepancies in Radioimmunoassay for Digoxin in Human Serum

Abstract In our series of 73 patients, definite indications of toxicity were always associated with a serum digoxin concentration of 2.0 ng/ml or higher, while in the possibly intoxicated and nonintoxicated patients only 24% and 10%, respectively, had a concentration this high. The nonintoxicated patients included significantly more with subnormal serum albumin concentrations. In vitro addition of radiolabeled digoxin and antibody showed that sera from many patients with hypoalbuminemia will enhance the binding of the label, which could result in a digoxin radioimmunoassay value as much as threefold low. These results were unrelated to other serum constituents, including the associated hyperglobulinemia, or to methodologic problems in the immunoassay. The proportion of digoxin bound to serum proteins was not significantly different between the normal (38% ± 3%) and hypoalbuminemic (31% ± 3%) individuals, and so this could not explain the difference in the assay results. We conclude that patients whose serum albumin concentrations are low may show erroneously low radioimmunoassay values for serum digoxin, and that this may explain why some patients receiving high doses of digoxin are found to have unexpectedly low apparent concentrations of digoxin in their serum.

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Serum Concentration and Serum Half-Life of Digoxin in Premature and Mature Newborns

PEDIATRICS ◽

10.1542/peds.59.6.902 ◽

1977 ◽

Vol 59 (6) ◽

pp. 902-906

Author(s):

Dieter Lang ◽

Götz von Bernuth

Keyword(s):

Renal Function ◽

Premature Infants ◽

Half Life ◽

Digoxin Concentration ◽

Serum Digoxin Concentration ◽

Serum Concentrations ◽

Premature Newborns ◽

Serum Digoxin ◽

Median Serum ◽

The Difference

Serum concentrations and half-life times of digoxin were determined in ten mature and nine premature newborns. Median serum digoxin concentration was 2.3 ng/ml (1.2 to 3.5 ng/ml) in mature newborns and 2.4 ng/ml (1.5 to 4.5 ng/ml) in premature newborns. Median serum digoxin half-life was 35 hours (17 to 52 hours) in mature newborns and 57 hours (38 to 88 hours) in premature newborns. The difference in serum digoxin half-life between the two groups is statistically significant. The relatively long serum digoxin half-life in premature newborns is probably due to immature renal function in this group. The data emphasize the need for cautious digoxin administration, especially in premature infants.

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Digoxin–amiodarone interaction: in vivo and in vitro studies in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y83-212 ◽

1983 ◽

Vol 61 (12) ◽

pp. 1483-1486 ◽

Cited By ~ 7

Author(s):

G. Koren ◽

S. Soldin ◽

S. M. Macleod

Keyword(s):

Digoxin Concentration ◽

Fold Increase ◽

Serum Digoxin Concentration ◽

Digoxin Interaction ◽

Diaphragmatic Muscle ◽

Serum Digoxin ◽

Cardiac Disorders ◽

Renal Tubular

Amiodarone is a new antiarrhythmic drug, commonly coadministered with digoxin in various cardiac disorders. Amiodarone caused a 10-fold increase of serum digoxin in rats, when the two drugs were simultaneously administered. Amiodarone significantly reduced digoxin uptake by renal cortical slices in the rat, and failed to reduce digoxin uptake by either heart or diaphragmatic muscle. The inhibition of the renal tubular uptake of digoxin caused by amiodarone may explain in part the increased serum digoxin concentration observed in vivo. Close resemblance was found between the mechanisms involved in the amiodarone–digoxin interaction, and those of digoxin interaction with either quinidine or verapamil.

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Improved Detection of Candida sp.fksHot Spot Mutants by Using the Method of the CLSI M27-A3 Document with the Addition of Bovine Serum Albumin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01350-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 2245-2255 ◽

Cited By ~ 26

Author(s):

Guillermo Garcia-Effron ◽

Steven Park ◽

David S. Perlin

Keyword(s):

Bovine Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Bovine Serum ◽

Serum Proteins ◽

Hot Spot ◽

Surrogate Marker ◽

Wild Type ◽

Content Type

ABSTRACTEchinocandins are highly bound to serum proteins, altering their antifungal properties. The addition of 50% human serum to the MIC assay improves the identification of echinocandin-resistantCandidaspp. harboringfkshot spot mutations. However, this modification cannot readily be applied to the method of the CLSI M27-A3 document due to safety and standardization difficulties. The aim of this study was to evaluate commercial bovine serum albumin (BSA) as a safe and standardized alternative to human serum. A collection of 28 echinocandin-susceptible strains, 10Candida parapsilosissensu lato strains (with naturally reduced echinocandin susceptibility), and 40FKShot spot mutants was used in this work. When RPMI 1640 was used for susceptibility testing, wild-type strains andfksmutants showed MIC range overlaps (−2, −1, and −3 2-fold-dilution steps separated these populations for anidulafungin, caspofungin, and micafungin, respectively). On the other hand, the addition of BSA to RPMI 1640 differentially increased echinocandin MIC values for these groups of strains, allowing better separation between populations, with no MIC range overlaps for any of the echinocandin drugs tested. Moreover, the use of RPMI-BSA reduced the number offkshot spot mutant isolates for which MIC values were less than or equal to the upper limit for the wild type (very major errors) from 9, 2, and 7 with RPMI alone to 3, 0, and 3 for anidulafungin, caspofungin, and micafungin, respectively. When RPMI-BSA was used to study the susceptibility ofC. parapsilosissensu lato species to echinocandins, the strains behaved as anidulafungin- and micafungin-resistant isolates (MIC, ≥8 μg/ml). These data support the need for a revision of the CLSI protocol forin vitrotesting of echinocandin susceptibility in order to identify all or most of thefkshot spot mutants. Also, caspofungin could be used as a surrogate marker of reduced susceptibility to echinocandins.

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A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo

Microorganisms ◽

10.3390/microorganisms8101627 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1627

Author(s):

Tecla Ciociola ◽

Pier Paolo Zanello ◽

Tiziana D’Adda ◽

Serena Galati ◽

Stefania Conti ◽

...

Keyword(s):

Antifungal Activity ◽

Human Serum ◽

Fungicidal Activity ◽

Galleria Mellonella ◽

Serum Proteins ◽

Morphological Alterations ◽

C Terminus ◽

Different Sources

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

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Study on the interaction of ertugliflozin with human serum albumin in vitro by multispectroscopic methods, molecular docking, and molecular dynamics simulation

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2019.04.047 ◽

2019 ◽

Vol 219 ◽

pp. 83-90 ◽

Cited By ~ 14

Author(s):

Wenjing Wang ◽

Na Gan ◽

Qiaomei Sun ◽

Di Wu ◽

Ruixue Gan ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Dynamics Simulation

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Nof2206Probing the interaction of memantine, an important Alzheimer's drug, with human serum albumin: In silico and In vitro approach

Journal of Molecular Liquids ◽

10.1016/j.molliq.2021.116888 ◽

2021 ◽

pp. 116888

Author(s):

Fahad A. Alhumaydhi ◽

Mohammad Abdullah Aljasir ◽

Abdullah S.M. Aljohani ◽

Suliman A. Alsagaby ◽

Ameen S.S. Alwashmi ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

In Silico

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Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

Pharmaceuticals ◽

10.3390/ph14010022 ◽

2020 ◽

Vol 14 (1) ◽

pp. 22

Author(s):

Kenji Tsukigawa ◽

Shuhei Imoto ◽

Keishi Yamasaki ◽

Koji Nishi ◽

Toshihiko Tsutsumi ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Coupling Reaction ◽

Synthetic Polymer ◽

Ph Sensitive ◽

Acidic Ph ◽

Polymer Conjugate ◽

Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

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A Precipitin-like Reaction of the Hemolymph of the Lobster Homarus americanus

Journal of the Fisheries Research Board of Canada ◽

10.1139/f69-127 ◽

1969 ◽

Vol 26 (5) ◽

pp. 1392-1397 ◽

Cited By ~ 10

Author(s):

James E. Stewart ◽

Diane M. Foley

Keyword(s):

Bovine Serum Albumin ◽

Serum Albumin ◽

Bovine Serum ◽

Serum Proteins ◽

Homarus Americanus ◽

Test Period ◽

Fluorescent Material

The levels of fluorescent material in the hemolymph of lobsters injected with serum proteins from lobster hemolymph labelled with fluorescein remained relatively constant over a 6-day test period; the levels in lobsters injected with bovine serum albumin labelled with fluorescein declined rapidly. A precipitin-like reaction was observed when lobster hemolymph serum was titrated with bovine serum albumin in vitro.

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