Determination of unbound antiretroviral drug concentrations by a modified ultrafiltration method reveals high variability in the free fraction.

Details

Serval ID
serval:BIB_14181C037D30
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Determination of unbound antiretroviral drug concentrations by a modified ultrafiltration method reveals high variability in the free fraction.
Journal
Therapeutic drug monitoring
Author(s)
Fayet A., Béguin A., de Tejada B.M., Colombo S., Cavassini M., Gerber S., Eap C.B., Telenti A., Buclin T., Biollaz J., Decosterd L.A.
ISSN
0163-4356 (Print)
ISSN-L
0163-4356
Publication state
Published
Issued date
08/2008
Peer-reviewed
Oui
Volume
30
Number
4
Pages
511-522
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Total plasma concentrations are used for therapeutic drug monitoring of antiretroviral drugs, whereas antiviral activity is expected to depend on unbound concentrations. The determination of free (unbound) concentrations by ultrafiltration may be flawed by the irreversible adsorption of many drugs onto the membrane filters and plastic components of the device. The authors describe a modified ultrafiltration method enabling the accurate measurement of unbound concentrations of 10 antiretroviral drugs by liquid chromatography-tandem mass spectroscopy, which circumvents the problem of loss by adsorption in the early ultrafiltration fractions. The method was applied to assess the variability of free fractions of antiretroviral drugs during routine therapeutic drug monitoring in 144 patients with HIV. In in vitro experiments, ultrafiltrate collected in four fractions (0-8, 8-16, 16-24, and 24-30 minutes) gave much lower and more variable free drug concentrations in the first ultrafiltrate fraction than in the last three fractions for lopinavir, nelfinavir, saquinavir, tipranavir, and efavirenz. In the last two fractions, free concentrations remained constant, indicating saturable adsorption. The adsorption was modest for indinavir, amprenavir, and ritonavir, and unnoticeable for atazanavir and nevirapine. Free fraction values obtained with this modified ultrafiltration method reveal substantial interindividual variability, suggesting that monitoring unbound antiretroviral drug concentrations may increase its clinical usefulness, especially for lopinavir, saquinavir, and efavirenz.

Keywords
Anti-HIV Agents/blood, Anti-HIV Agents/therapeutic use, Antiretroviral Therapy, Highly Active, Calibration, Chromatography, High Pressure Liquid, HIV Infections/blood, HIV Infections/drug therapy, Hemoglobin A, Glycosylated/analysis, Humans, Indicators and Reagents, Quality Control, Serum Albumin/analysis, Tandem Mass Spectrometry, Ultrafiltration
Pubmed
Web of science
Create date
17/10/2008 14:38
Last modification date
20/08/2019 12:42
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