کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5833479 | 1122624 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Determination of P-glycoprotein surface expression and functional ability after in vitro treatment with darunavir or raltegravir in lymphocytes of healthy donors
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
FITCNRTIsNNRTIPBMCsAPCHAARTMFIMDRDMSO - DMSOhighly active antiretroviral therapy - درمان ضد رتروویروسی بسیار فعالDimethylsulfoxide - دیمتیل سولفواکسیدperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیmedian fluorescence intensity - شدت فلورسانس متوسطMulti-drug resistance - مقاومت چند داروییIntegrase inhibitor - مهار کننده انتگرالNucleoside reverse transcriptase inhibitors - مهار کننده های ترانس کپسول معکوس نوکلئوزیدNon-Nucleoside Reverse Transcriptase Inhibitors - مهار کننده های ترانسپرتالس معکوس غیر هسته ای
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
It has been shown that P-glycoprotein (P-gp) can greatly affect the cell uptake of antiretroviral drugs, thus hampering their access to HIV-1 replication sites. Lymphocytes are important sites of replication of HIV and target of other drugs, modification on these cells of P-gp could have an effect on pharmacokinetic of antiretrovirals and drug substrates. Blood samples from 16 healthy volunteers were used to determine the expression of P-gp on total, T and T helper lymphocytes after exposure to darunavir, a second generation protease inhibitor, and raltegravir, the first approved integrase inhibitor. Moreover, the effect of the drugs on P-gp functional activity was also studied by the rhodamine-123 efflux test. Darunavir, but not raltegravir, exposure caused a moderate, dose-dependent increment in P-gp expression in total, T and T helper lymphocytes, as demonstrated by the relative frequency of P-gp + cells and by the amount of P-gp molecules present on cell surface. Functionally, incubation with darunavir led to a marked inhibition of P-gp activity measured by the efflux of rhodamine-123 similar to that observed by verapamil, a specific P-gp inhibitor. Raltegravir was not able to modify the efflux of rhodamine-123 level. Data show that darunavir, unlike raltegravir, may modify the expression and functionality of P-gp on human lymphocytes, thus leading to potential changes in intracellular concentrations of darunavir in patients treated with other drugs substrate of P-gp and vice versa. Our study highlights the need for studies on drug interactions via the P-gp modulation mechanism, especially with the current multi-drug regimens.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 16, Issue 4, August 2013, Pages 492-497
Journal: International Immunopharmacology - Volume 16, Issue 4, August 2013, Pages 492-497
نویسندگان
Massimo Tempestilli, Elisa Gentilotti, Chiara Tommasi, Emanuele Nicastri, Federico Martini, Pasquale De Nardo, Pasquale Narciso, Leopoldo P. Pucillo,