Are plasma levels valid surrogates for cellular concentrations of antiretroviral drugs in HIV-infected patients?

Details

Serval ID
serval:BIB_34514467D3D9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Are plasma levels valid surrogates for cellular concentrations of antiretroviral drugs in HIV-infected patients?
Journal
Therapeutic Drug Monitoring
Author(s)
Colombo  S., Telenti  A., Buclin  T., Furrer  H., Lee  B. L., Biollaz  J., Decosterd  L. A.
ISSN
0163-4356 (Print)
Publication state
Published
Issued date
06/2006
Volume
28
Number
3
Pages
332-8
Notes
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't --- Old month value: Jun
Abstract
Total plasma concentrations are currently measured for therapeutic drug monitoring of HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). However, the pharmacological target of antiretroviral drugs reside inside cells. To study the variability of their cellular accumulation, and to determine to which extent total plasma concentrations (TPC) correlate with cellular concentrations (CC), plasma and peripheral blood mononuclear cells (PBMCs) were simultaneously collected at single random times after drug intake from 133 HIV infected patients. TPC levels were analysed by high-performance liquid chromatography with ultraviolet detection and CC by LC-MS/MS from peripheral blood mononuclear cells. The best correlations between TPC and CC were observed for nelfinavir (NFV, slope=0.93, r=0.85), saquinavir (SQV, slope=0.76, r=0.80) and lopinavir (LPV, slope=0.87, r=0.63). By contrast, TPC of efavirenz (EFV) exhibited a moderate correlation with CC (slope=0.69, r=0.58), while no correlation was found for nevirapine (NVP, slope=-0.3, r=0.1). Interindividual variability in the CC/TPC ratio was lower for protease inhibitors (coefficients of variation 76%, 61%, and 80% for SQV, NFV and LPV, respectively) than for nonnucleoside reverse transcriptase inhibitors (coefficients of variation 101% and 318%, for EFV and NVP). As routine CC measurement raises practical difficulties, well-correlated plasma concentrations (ie, NFV, SQV and LPV) can probably be considered as appropriate surrogates for cellular drug exposure. For drugs such as EFV or NVP, there may be room for therapeutic drug monitoring improvement using either direct CC determination or other predictive factors such as genotyping of transporters or metabolizing enzyme genes.
Keywords
Adult Anti-HIV Agents/*blood/pharmacokinetics Cohort Studies Drug Monitoring/*methods Female HIV Infections/*blood/*drug therapy HIV Protease Inhibitors/blood/pharmacokinetics Humans Leukocytes, Mononuclear/metabolism Male Middle Aged Reverse Transcriptase Inhibitors/*blood/pharmacokinetics
Pubmed
Web of science
Create date
25/01/2008 11:41
Last modification date
20/08/2019 14:20
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