Measuring the unbound concentration fails to resolve analytic interferences in digoxin immunoassays

Simple item page
dc.contributor.authorMorris, R.
dc.contributor.authorJones, T.
dc.contributor.authorWicks, F.
dc.contributor.authorRogers, N.
dc.date.issued2008
dc.description.abstractTherapeutic drug monitoring of digoxin is well established in the clinical management of cardiac patients treated with the drug. Recently, target concentrations have been revised in patients with congestive heart failure to 0.5 to 0.8 μg/L, challenging the sensitivity limits of most immunoassays. These widely used methods are often criticized, particularly on specificity grounds resulting from interference from exogenous and endogenous sources. One solution to remove higher molecular weight interference has been to ultrafilter plasma samples before assaying. The present study included 261 patient digoxin samples and compared two commercial ultrafiltration devices (Centrifree and Micrcon) that share the same separation membrane (YM-30). The results showed widely discordant apparent unbound digoxin concentrations in the ultrafiltrate from these devices with a Deming regression line of Centrifree = 1.31 X Micrcon + 0.042 (95% confidence interval for slope of 1.237 to 1.391) and apparent unbound fractions ranging from 15% to 610% of the unfiltered plasma digoxin concentrations, suggesting that ultrafiltration did not resolve such interference issues. The concept of measuring lower unbound digoxin concentrations as a result of lower therapeutic range for total (bound plus unbound) digoxin will also render most immunoassays insensitive and inappropriately calibrated. There is a strong imperative to review digoxin monitoring practices in the light of current clinical imperatives for both specificity and sensitivity reasons.
dc.description.statementofresponsibilityRaymond G. Morris, Terry E. Jones, Fiona A. Wicks, Natasha M. Rogers
dc.identifier.citationTherapeutic Drug Monitoring, 2008; 30(4):548-552
dc.identifier.doi10.1097/FTD.0b013e3181783ef1
dc.identifier.issn0163-4356
dc.identifier.issn1536-3694
dc.identifier.urihttp://hdl.handle.net/2440/52436
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.source.urihttp://journals.lww.com/drug-monitoring/Abstract/2008/08000/Measuring_the_Unbound_Concentration_Fails_to.22.aspx
dc.subjectHumans
dc.subjectDigoxin
dc.subjectCardiotonic Agents
dc.subjectImmunoassay
dc.subjectSpecimen Handling
dc.subjectBlood Specimen Collection
dc.subjectUltrafiltration
dc.subjectCalibration
dc.subjectRegression Analysis
dc.subjectProtein Binding
dc.titleMeasuring the unbound concentration fails to resolve analytic interferences in digoxin immunoassays
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Pharmacology publications