کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1968534 | 1538862 | 2016 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Quantification of darunavir and etravirine in human peripheral blood mononuclear cells using high performance liquid chromatography tandem mass spectrometry (LC–MS/MS), clinical application in a cohort of 110 HIV-1 infected patients and evidence of a pote Quantification of darunavir and etravirine in human peripheral blood mononuclear cells using high performance liquid chromatography tandem mass spectrometry (LC–MS/MS), clinical application in a cohort of 110 HIV-1 infected patients and evidence of a pote](/preview/png/1968534.png)
• Virological failure is still encountered in daily clinical practice.
• An analytical method allowing the quantification of antiretroviral drugs in target cells might be of clinical relevance.
• A handy and sensitive LC–MS/MS method allowing the simultaneous quantification of DRV and ETR in PBMCs has been validated.
• The intracellular pharmacokinetic of DRV and ETR in clinical setting is described.
• Our data highlight a possible impact of ETR co-administration and eGFR on DRV plasma concentrations.
ObjectivesTo describe the validation of a sensitive high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method allowing the simultaneous quantification of darunavir (DRV) and etravirine (ETR) in peripheral blood mononuclear cells (PBMCs) and its application in a cohort of HIV-1 infected patients.MethodsBlood samples were obtained from 110 patients. PMBCs were isolated using density gradient centrifugation. Drug extraction from PBMCs was performed with a 60:40 methanol–water (MeOH–H2O) solution containing deuterated IS (DRV-d9 and ETR-d8). The chromatographic separation was performed on a RP18 XBridge™ column.ResultsThe geometric mean (GM) of cell associated concentration ([DRV]CC) and plasmatic concentration ([DRV]plasma) were 360.5 ng/mL (CI95%:294.5–441.2) and 1733 ng/mL (CI95%:1486–2021), respectively. A geometric mean intracellular (IC)/plasma ratio (GMR) of 0.21 (CI95%:0.18–0.24) was calculated. Adjusted for dose/body surface area and post-intake time, a statistically significant correlation was observed between [DRV]Plasma and the eGFR (p = 0.002) and between [DRV]Plasma and the concomitant use of ETR (p = 0.038). For the 10 patients receiving ETR in addition to DRV, the GM of [ETR]Plasma (available for 8 out of 10 patients) and [ETR]CC were 492.3 ng/mL and 2951 ng/mL respectively. The GMR of ETR was 7.6 (CI95%: 3.61–13.83).ConclusionsA handy and sensitive high performance LC–MS/MS method allowing the simultaneous quantification of DRV and ETR in PBMCs has been described and successfully applied in the largest cohort of DRV-treated patients reported to date. ETR accumulates more efficiently in PBMCs compared to DRV. We have also highlighted a possible impact of ETR on DRV plasma concentrations requiring further investigations.
Journal: Clinical Biochemistry - Volume 49, Issues 7–8, May 2016, Pages 580–586