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PubMed1992

Glycyrrhizin binding site on human serum albumin.

The binding site of glycyrrhizin (GLZ) on human serum albumin was detected through competitive displacement experiments with GLZ and ibuprofen (IBU) (diazepam site), warfarin (WAR), salicylate (SAL) (digitoxin site), or deoxycholic acid (DCA) by means of an ultrafiltration technique. The specific binding of GLZ was subject to competitive inhibition by IBU, WAR, SAL, or DCA (1 or 4 mM). The extent of displacement was in the order of: DCA greater than IBU greater than WAR greater than SAL. Conversely, the specific bindings of WAR and DCA and the low-affinity bindings of IBU and SAL were subject to competitive inhibition by GLZ (1 or 4 mM). The extent of inhibition by GLZ was in the order of DCA greater than IBU greater than WAR not equal to SAL. In addition, the low-affinity IBU binding and the specific DCA binding showed mutual competitive inhibition at 4 mM, with almost identical displacements. It was concluded that the specific GLZ binding site on human serum albumin may be located mostly within the low-affinity IBU binding site area (probably the same as the specific DCA binding site area) and partially within the specific WAR binding site area and the low-affinity SAL binding site area.

Binding Sites↗
PubMed1992

Studies on cardiac ingredients of plants. IX. Chemical transformation of proscillaridin by utilizing its 1,4-cycloadducts as key compounds and biological activities of their derivatives.

Three aromatic compounds (2-4) possessing a carbomethoxyl group or a dimethoxyphthaloyl group, prepared by the Diels-Alder reaction of the cardiac glycoside, proscillaridin (1), with dimethyl acetylenedicarboxylate and methyl propiolate, were transformed into alcohols, carboxylic acids and amides. The biological activities of the resulting derivatives were evaluated by the use of Na+, K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) from dog kidney and isolated guinea-pig papillary muscle. Although the biological activities of the resulting derivatives were less potent than that of 1, a para-substituted benzylalcohol (5), methylbenzamides (9a and 10a), and ethylbenzamides (9b and 10b) inhibited the activity of Na+,K(+)-ATPase almost as potently as naturally occurring cardiac glycosides such as digoxin and digitoxin.

Animals↗
PubMed1995

Studies on differentiation inducers. V. Steroid glycosides from periplocae radicis cortex.

Six pregnane glycosides and three cardenolides were isolated as differentiation inducers using mouse myeloid leukemia (Ml) cells from Periplocae Radicis Cortex (bark of Periploca sepium BGE., Asclepiadaceae). The cardenolides showed much higher activities than the pregnane glycosides. Besides these nine compounds, commercially available cardenolides were tested for their differentiation inducing activities using Ml cells. Digitoxin and digoxin induced Ml cells into phagocytic cells, but others did not. In the presence of 1 nM of actinomycin-D, the activity of steroid glycosides was enhanced against Ml cells.

Animals↗
PubMed1998

Some properties and the inclusion behavior of three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaoses (beta-cyclodextrins).

Three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaose [1,n-(G)2-beta CDs; n = 2-4] which existed in the digests with glucoamylase of the products from cyclomaltoheptaose (beta-cyclodextrin, beta CD) and maltose with Klebsiella pneumoniae pullulanase, were purified by HPLC. The solubilities of two isomers of those doubly branched beta CDs, 1,2- and 1,3-(G)2-beta CDs, in water were much higher than those of parent non-branched beta CD and mono-branched beta CD, 6-O-alpha-D-glucosyl-beta CD (G-beta CD), while the solubility of another isomer, 1,4-(G)2-beta CD, was significantly lower than these two isomers, though it was higher than that of beta CD. On the other hand, the solubilities of 1,2- and 1,3-isomers in 10, 30, and 50% (v/v) aqueous methanol at 25 degrees C were independent of methanol concentrations and their solubilities were the same as those in water at 25 degrees C. However, that of 1,4-isomer increased with increasing methanol concentrations. The hemolytic activities of 1,n-(G)2-beta CDs on human erythrocytes in isotonic solution were lower than those of G-beta CD and beta CD, and became weaker in the order of 1,4- > 1,2- > 1,3-isomers. The complex-forming abilities of 1,n-(G)2-beta CDs for digitoxin, digoxin, fluorometholone, flurbiprofen, hydrocortisone acetate, and norfloxacin were about the same as those of beta CD and G-beta CD, whereas reserpine was more difficult to include within 1,n-(G)2-beta CDs than beta CD and G-beta CD. Nevertheless, the solubilities of those guest compounds were much more enhanced by 1,n-(G)2-beta CDs and G-beta CD than by beta CD.

Chemical Phenomena↗
PubMed1992

[Effects of bufadienolides and some kinds of cardiotonics on guinea pig hearts].

Effects of bufadienolides such as bufalin (BF) and cinobufagin (CB), the main components of Senso (Ch'an Su), on myocardial Na+,K(+)-ATPase activity, the cardiotonic activity in vivo and the action potential of isolated guinea pig papillary muscle cells were compared with those of other cardiotonic drugs. 1) The rank order of potency for inhibition of myocardial Na+,K(+)-ATPase activity was BF greater than digoxin (DG) greater than digitoxin (DT) greater than telocinobufagin greater than gamabufotalin greater than cinobufotalin greater than CB greater than g-strophanthin (GS) greater than digitoxigenin (DTG) greater than resibufogenin (RB) when compared at the 50% inhibitory concentration. 2) In isolated papillary muscle cells, CB shortened the action potential duration (APD) dose-dependently. The order of potency for shortening of APD was GS greater than CB greater than DTG much greater than DT. 3) In open-chest guinea pigs, intraduodenal administration of BF or CB increased the myocardial contractile force (MCF), but did not affect the heart rate. The order of potency for increase in MCF was as follows: methyldigoxin, proscillaridin greater than BF greater than CB greater than DG greater than Senso much greater than DT, DTG, RB. These results indicate that CB has a shortening effect on APD and an inhibitory effect on Na+,K(+)-ATPase activity along with its cardiotonic effect, like GS.

Action Potentials↗
PubMed1988

Palytoxin-induced K+ efflux from ileal longitudinal smooth muscle of the guinea-pig.

In guinea-pig ileal longitudinal smooth muscle, both palytoxin (PTX) and carbachol (CCh) increased K+ efflux with an EC50 of 1.8 X 10(-10) M and 4.1 X 10(-7) M, respectively. Atropine (10(-6) M) did not inhibit the K+ efflux due to PTX (3 X 10(-9) M), but completely inhibited the efflux due to CCh (10(-5) M). External Ca2+ removal and verapamil (10(-5) M) did not change the PTX-induced K+ efflux, although the CCh-induced K+ efflux was inhibited about 77% and 71%, respectively. PTX-induced K+ efflux was reduced to 31% by a depletion of intracellular Ca2+. Tetraethylammonium (15 mM) inhibited the K+ efflux due to PTX or CCh to 61% or 75%, respectively. The PTX-induced K+ efflux was also inhibited by cymarin (3 X 10(-8) M), ouabain (10(-5) M) and digitoxin (10(-5) M). These results suggest that the PTX-induced K+ efflux is less dependent on Ca2+ influx than that due to CCh. Furthermore, the binding sites for PTX in the ileal muscle of guinea-pig may be Na+, K+-ATPase, as has been suggested in other types of cells.

Acrylamides↗
PubMed2001

Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies.

A group of international experts prepared two lists of drugs with their serum/plasma and urine concentrations, which should be used when evaluating the performance of a new laboratory method. The two lists were verified by running in vitro interference studies in three European laboratories on Hitachi instruments. The study identified the following new interferants: acid phosphatase in serum by ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline, levodopa, methyldopa and metronidazole; digitoxin in serum by rifampicin; phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline; theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa, phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline, levodopa, rifampicin and phenylbutazone; valproic acid in serum by phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid factor in serum by ibuprofen and metronidazole; pancreatic amylase and total amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin, levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine, gentamicin and methyldopa; beta2-microglobulin in urine by ascorbic acid; total protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference in acid phosphatase, creatine kinase MB and bilirubin methods was observed at very low analyte concentrations, and therefore it may not be evident at higher concentrations. The study confirmed the usefulness of the recommendation.

Blood Chemical Analysis↗
PubMed2006

Effect of plantain on therapeutic drug monitoring of digoxin and thirteen other common drugs.

INTRODUCTION: Plantain, a herbal remedy, has been reported to interfere with therapeutic drug monitoring of digoxin. We evaluated three commercially available plantain products for potential interference with therapeutic drug monitoring of digoxin and 13 other common drugs. METHOD: Dry content of plantain capsule or plantain leaf was extracted with either methanol or ethanol:water (60:40 by volume), added to drug-free serum and apparent digoxin was measured by both fluorescence polarization immunoassay and microparticle enzyme immunoassay. Using immunoassays, we also measured apparent concentrations of 13 other drugs (tobramycin, procainamide, tricyclic antidepressants, quinidine, carbamazepine, phenytoin, theophylline, valproic acid, amikacin, gentamycin, phenobarbital, salicylate and acetaminophen [paracetamol]) due to the presence of plantain. In separate experiments, a serum pool prepared from patients receiving digoxin was further supplemented with plantain and observed digoxin values were compared with original digoxin concentration. The presence of any cardiac glycoside in plantain was also investigated using thin layer chromatography (TLC). RESULTS: We observed no apparent digoxin in the presence of plantain in serum. Moreover, when aliquots of digoxin serum pool were supplemented with various amounts of plantain, the observed digoxin concentrations in the presence of plantain compared well with original digoxin concentration. TLC analysis did not show the presence of either digoxin or digitoxin in plantain products studied. Moreover, plantain did not affect immunoassay results of the 13 other drugs studied. CONCLUSIONS: The plantain products studied did not interfere with therapeutic drug monitoring of digoxin as well as 13 other commonly monitored drugs.

Cardiac Glycosides↗
PubMed2004

Fab antibody fragments: some applications in clinical toxicology.

This review provides current information on the use of antigen-binding fragments (Fab) from cleaved antibodies to treat poisoning with digoxin and other potent, low formula mass poisons, such as colchicine and tricyclic antidepressants. Anti-digoxin Fab fragments have been used successfully for many years in the management of severe poisoning with digoxin, digitoxin, and a range of other structurally related compounds, including cardiotoxins from Nerium and Thevetia sp. (oleander) and Bufo sp. (toads). However, their main use remains treating digoxin poisoning. Equimolar doses of anti-digoxin Fab fragments completely bind digoxin in vivo. The approximate dose of Fab fragments (mg) is 80 times the digoxin body burden (mg). If neither the dose ingested nor the plasma digoxin/digitoxin concentration is known, in an adult 380 mg of anti-digoxin Fab fragments should be given. The dose for elderly patients or those with renal impairment should be similar to that for those with normal renal function. Fab fragments have a plasma half-life of 12-20 hours, but this can be prolonged in patients with renal impairment. Analysis of serum ultrafiltrate using an immunoassay shown not to have matrix bias remains the most accurate approach to measuring free digoxin in the presence of anti-digoxin Fab fragments. The antibody fragments are given intravenously over 15-30 minutes after dilution to at least 250 mL with plasma protein solution, 0.9% (w/v) sodium chloride, or deionised water, except in infants where the volume infused can be reduced. Factors limiting the efficacy of Fab fragments are the dose, the duration of the infusion and any delay in administration. Guidelines for Fab fragment administration in children include (i) dilution to a final Fab concentration of 10 g/L in either 5% (w/v) dextrose or 0.9% (w/v) sodium chloride; (ii) infusion through a 0.22 microm filter; (iii) administration of the total dose over a minimum of 30 minutes; and (iv) avoiding coadministration of other drugs and/or electrolyte solutions. Fab fragments are generally well tolerated. Adverse effects attributable to Fab treatment include hypokalaemia and exacerbation of congestive cardiac failure; renal function could be impaired in some patients. Fab fragment preparations for treating acute colchicine and tricyclic antidepressant poisoning have been developed, but are not available commercially. Colchicine poisoning is rare in Western countries, and pharmacological management together with supportive care is usually effective even in severe tricyclic antidepressant overdosage. Attempts have been made to produce anti-paraquat antibodies capable of enhancing paraquat elimination from the lung, but thus far all such attempts have proved unsuccessful.

Digoxin↗
PubMedDate not supplied

Effect of cardiopulmonary bypass on the pharmacokinetics of drugs.

The cardiopulmonary bypass apparatus must temporarily substitute for the cardiac and pulmonary function of the patient undergoing heart surgery. In order to meet the metabolic needs of the patient and the technical demands of the surgeon, within the limits of engineering technology, a number of major alterations are made in normal physiology. The patient is typically cooled to 27 degrees C and perfused with a non-pulsatile flow of blood which has been diluted with saline to a haematocrit in the mid-20s. Blood flow and pressure are often considerably less than normal. Blood coagulation is prevented by administration of a massive dose of heparin. Central redistribution of blood flow, elaboration of stress-reactant hormones, and fluid and electrolyte shifts occur in response to these changes. In the postoperative period, these alterations are reversed, and normal physiology is restored. Effects upon the pharmacokinetics of drugs are anticipated. The clearance of many drugs may be reduced. Protein binding is diminished by haemodilution, but may rise above normal in the postoperative period for basic drugs which bind to alpha 1-acid glycoprotein. Changes in volume of distribution depend upon the opposing influences of protein binding and reduced peripheral perfusion. Previous studies on the pharmacokinetics of drugs during and after cardiopulmonary bypass illustrate many of these effects. The clearance of digoxin, fentanyl, and the cephalosporins is reduced after cardiopulmonary bypass, and the volume of distribution of cefazolin is increased during cardiopulmonary bypass. Studies of digitoxin and propranolol are also reviewed. Many of the investigations in this area of study have been limited by logistical and methodological factors. Thus, the effects of cardiopulmonary bypass on the pharmacokinetics of drugs are incompletely understood, and the subject merits further attention.

Animals↗
PubMed1990

Effects of antacids on the clinical pharmacokinetics of drugs. An update.

Since a previous review by Hurwitz was published in 1977 a large number of reports on drug interactions with antacids have appeared, few of which are of clinical relevance. Tetracyclines form insoluble complex molecules by metal ion chelation with various antacids; tetracycline absorption may be decreased by more than 90% by this interaction. Of the new class of quinolone antibiotics, the absorption of ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of aluminium- and magnesium hydroxide-containing antacids. In contrast to early work showing inhibition of the absorption of beta-adrenergic blocking drugs by antacids, subsequent studies did not confirm a reduction in the bioavailability of either atenolol or propranolol during antacid treatment; indeed, they showed an increase in the plasma concentrations of metoprolol when the drug was coadministered with an antacid. The bioavailability of captopril was significantly reduced in the presence of an antacid, and lower plasma concentrations of this angiotensin-converting enzyme inhibitor were accompanied by a reduction of its effect on the systolic blood pressure of the patients. The absorption of the cardiac glycosides digoxin and digitoxin is not inhibited by antacids to a significant degree, although earlier studies had shown a positive effect when the dissolution of the glycoside preparations was relatively poor. Antacids reduce the bioavailability of the H2-receptor antagonists cimetidine and ranitidine only when high antacid doses are used and when the drugs are administered simultaneously. The bioavailability of famotidine was not significantly altered by a potent antacid preparation, although a trend towards reduced absorption was observed. Iron absorption is significantly decreased in the presence of sodium bicarbonate and calcium carbonate, but is nearly complete when coadministered with aluminium-magnesium hydroxide. Nonsteroidal anti-inflammatory drugs such as naproxen, tenoxicam, ketoprofen, ibuprofen and piroxicam are not affected in their absorption by antacid treatment. Theophylline bioavailability is unchanged when the drug is given together with antacids, although its rate of absorption may be altered, leading to a reduction or an increase in the time of the occurrence of peak plasma drug concentrations.

Adrenergic beta-Antagonists↗
PubMed1993

Nimesulide binding to components within blood.

The binding of nimesulide within human serum to isolated proteins and to erythrocytes was studied by equilibrium dialysis. Within the range of therapeutic concentrations, nimesulide was 99% bound to serum involving a nonsaturated process (NKA = 91). This binding was almost identical to binding of nimesulide to serum albumin (NKA = 95). Physiological concentrations of free fatty acids did not affect binding of nimesulide to serum albumin. The retention of nimesulide by erythrocytes suspended in buffer was moderate (67%), although in whole blood no erythrocyte binding was observed because of the greater affinity of this drug for serum. Over the range of therapeutic concentrations (2.5 to 63 mumol/L), the free fraction of nimesulide in serum remains constant. Serum binding was decreased in samples obtained from patients with renal failure or hepatic cirrhosis associated with hypoalbuminaemia and hyperbilirubinaemia, respectively. At therapeutic concentrations, the binding of nimesulide was unaffected by warfarin, cefoperazone, furosemide (frusemide), glibenclamide, tamoxifen or digitoxin. However, valproic acid and fenofibrate (80 mumol/L) may displace nimesulide. 4-Hydroxy-nimesulide, the principal metabolite, significantly increased the free fraction of nimesulide. Although methotrexate had no effect on the free fraction of nimesulide, the free fraction of methotrexate was significantly increased in the presence of nimesulide. The present study also demonstrated 2 distinct nimesulide binding sites (site I and site II) on serum albumin (10 mumol/L) with different affinities: site II KA = 3.57 x 10(5) L/mol and site I KA = 1.24 x 10(5) L/mol. Interaction studies using markers that bind specifically to site I (warfarin and azapropazone) and site II (diazepam and ibuprofen) indicated that nimesulide binds to site II with higher affinity and to a lesser extent to site I.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1982

Light-dependent delta pH and membrane potential changes in halobacterial vesicles coupled to sodium transport.

Bacteriorhodopsin and Halorhodopsin present in Halobacterium halobium strains have been investigated in relation to Na+/H+ exchange in isolated cell envelope vesicles. Upon illumination, these retinal proteins result in extrusion of sodium ions by either an electrogenic Na+/H+ antiporter and/or a direct sodium pump. Since a molecular characterization of these mechanism(s) of sodium extrusion has not yet been realized, it was of interest to measure directly the light- and sodium-dependent changes in delta pH and membrane potential under nearly identical conditions in S9 and R1mR cell membrane vesicles to gain information on the relation of these retinal proteins to sodium extrusion. These activities were evaluated in terms of their dependence on light intensity, and on the inhibitory effect of chemical modifiers of carboxyl groups (carbodiimides); electroneutral exchanges (monensin and triphenyltin); digitoxin and some analogues; and phloretin. Under most of the conditions and treatments employed, light- and sodium-dependent delta pH led to similar effects in both membrane vesicle types. Hence, it is concluded that the delta pH and delta psi which arise from sodium transport occur by either a single mechanism or by one which shares common features.

Bacteriorhodopsins↗
PubMed1980

Arrhythmias and conduction disturbances following aortic valve implantation.

In the first postoperative week following aortic valve implantation, arrhythmias and conduction disturbances were seen in 37 of 44 patients studied. Sixty-seven episodes of arrhythmias occurred, atrial fibrillation and accelerated junctional rhythms accounted for more than 75% of these episodes. Episodes of atrial fibrillation were most common after the age of sixty.l When atrial premature contractions were observed, episodes of atrial fibrillation followed shortly afterwards. Accelerated junctional rhythms were seen in 17 patients and affected the patients haemodynamically when this dysrhythmia occurred early in the postoperative course, but improvements were seen promptly following atrial overpacing. Lidocaine was infused prophylactically for 2 days in patients with severe aortic stenosis or marked left ventricular hypertrophy. One episode of ventricular fibrillation and few incidents of ventricular extrasystoles were seen. Most conduction disturbances were transient, but bundle branch block persisted in 3 patients, and there was complete A-V block in a fourth. No causal relationship between the use of digitoxin and the frequency of arrhythmias could be established.

Adult↗
PubMed1992

In vitro studies of the efficacy of reversed phase silica gel as a sorbent for hemo- and plasmaperfusion.

The clearance capacities of reversed phase silica gel, widely used in analytical chemistry, were studied in vitro. The plasma clearances of amitriptyline, quinidine, digoxin, digitoxin, methaqualone, phenobarbital and phenytoin were determined at typical toxic plasma levels. Between 88.8 and 99.5% of the drugs were eliminated from plasma by reversed phase silica gel, which compares favorably with amberlite XAD-4 and coated activated charcoal. The biocompatibility of reversed phase silica gel was also evaluated in vitro. Thrombocytopenia and leukopenia were noted while coagulation parameters, electrolytes, acid-base balance, glucose, urea, creatinine, uric acid, total protein, albumin, bilirubin, cholesterol and triglycerides were not significantly affected. Preliminary results in vitro support the high clearance capacity of reversed phase silica gel and suggest a biocompatibility similar to that of other sorbents currently in use. Further investigation of the clearance capacities and biocompatibility of reversed phase silica gel seems justified.

Biocompatible Materials↗
PubMed1975

Ouabain plasma level kinetics and removal by dialysis in chronic renal failure. A study in fourteen patients.

Ouabain plasma level kinetics and removal by dialysis were studied in 14 dialysis-dependent patients with chronic renal failure. Each received one 400 mug intravenous dose of unlabeled ouabain (9 patients also received 83 muCi of 3-H-ouabain) at the onset of a routine 4-hour hemodialysis. Plasma concentration fell rapidly the first few hours, and after 5 to 10 hours declined exponentially with a mean half-life of 50 plus or minus 19 (SD) hours. Ouabain recovery in dialysis bath was 11.5% plus or minus 2.2% the first 2 hours and only 3.4% plus or minus 0.5% the next 2 hours after an intravenous dose, due to rapid removal of ouabain from the extracellular fluid compartment by tissue uptake. Hence, hemodialysis is relatively ineffective for reducing ouabain body stores. Ouabain elimination in patients with chronic renal failure is significantly slower than in normal subjects (P smaller than 0.01), but significantly more rapid than that reported for digoxin (P smaller than 0.01) and digitoxin (P smaller than 0.01) in patients with chronic renal failure, a potentially useful characteristic in treating acute cardiac problems among such patients.

Chromatography, Paper↗
PubMedDate not supplied

Non-pretreatment digoxin assays and developments in immunoanalyzers.

OBJECTIVE: The performance of a new, non-pretreatment digoxin assay for the Abbott IMx analyzer (Abbott Park IL) was evaluated to determine its reliability and suitability for routine clinical use. The operational characteristics of 1st, 2nd and 3rd generation immunoanalyzers are compared and contrasted. DESIGN: Within-run and day-to-day precision of the assay was determined, as well as its limit of detection. The effect of digoxin-like immunoreactive factors and carryover were evaluated. Serum from patients receiving digoxin was analyzed using the Dade Stratus II (Miami FL) digoxin test as the reference method and the IMx digoxin test as the comparison method. SETTING: An independent reference laboratory specializing in serving long-term care facilities. PATIENT POPULATION: Specimens were analyzed from geriatric patients in long-term care facilities who receive digoxin as a therapeutic drug for cardiac arrhythmias. Specimens were also tested from individuals in this same population, not receiving digoxin but demonstrating the presence of digoxin-like immunoreactive factors. MAIN OUTCOME MEASURE: Comparability of results from a new nonpretreatment digoxin with the standard digoxin assay (Stratus II) was used to determine the suitability of the new test for routine clinical use. RESULTS: The limit of detection is 0.27 ng/mL; day-to-day precision ranges from 3.4% CV to 5.9% CV. Linear regression analysis generated the following equation: IMx = 0.968 Stratus + 0.1043, r = 0.9776, n = 237. No significant interference from digitoxin-like immunoreactive factors was noted. CONCLUSION: The IMx nonpretreatment digoxin assay's performance matches the manufacturer's claims, compares favorably with another common automated digoxin test, and is suitable for routine clinical use.

Aged↗
PubMed1999

Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low detection limit.

A novel, highly sensitive and specific N-Terminal-proBNP (NT-proBNP) assay based on a sandwich format has been developed. The assay time is below 2 hours and no extraction process is needed. The calibration curve covers a NT-proBNP concentration range from 0 pmol/L up to 600 pmol/L. The analytical detection limit of the assay was estimated to be 2.7 pmol/L (3 SD). The intra-assay coefficient of variation is 5.7% (at 50 pmol/L) and 6.1% (at 250 pmol/L), while the inter-assay CVs are 15.8% (15 pmol/L) and 8.2% (250 pmol/L). There is no significant interference by bilirubin (up to 900 mumol/L), haemoglobin (up to 10 g/L), rheumatoid factors (up to 975 IU/mL), triglycerides (up to 20.5 mmol/L), biotin (up to 50 micrograms/L), digoxin (up to 100 micrograms/L) and digitoxin (up to 200 micrograms/L). The analyte NT-proBNP is fully stable in whole blood over 3 days and in EDTA-plasma over 24 hours. This good stability of NT-proBNP compared to other less stable natriuretic peptides is a significant advantage and a main prerequisite for a routine diagnostic marker. Preliminary results of using this new assay in clinical studies for diagnosing and monitoring left ventricular dysfunction demonstrate that there is a significant gain in diagnostic validity.

Antibodies, Monoclonal↗