ArticleBritish journal of clinical pharmacology2009
Intracellular 'boosting' of darunavir using known transport inhibitors in primary PBMC.
Article in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Comprehensive Study of Antiretroviral Drug Permeability at the Cervicovaginal MucosaPharmaceutics · 2022Article
- Knockout of ABC transporters by CRISPR/Cas9 contributes to reliable and accurate transporter substrate identification for drug discovery.Frontiers in pharmacology · 2022Article
- Article
- Differential expression of breast cancer-resistance protein, lung resistance protein, and multidrug resistance protein 1 in retinas of streptozotocin-induced diabetic mice.International journal of ophthalmology · 2017Article
- Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis.Antimicrobial agents and chemotherapy · 2015Article
- Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter.Frontiers in pharmacology · 2015Article
- Gag-Pol processing during HIV-1 virion maturation: a systems biology approach.PLoS computational biology · 2013Article
- Concentration-dependent effects and intracellular accumulation of HIV protease inhibitors in cultured CD4 T cells and primary human lymphocytes.The Journal of antimicrobial chemotherapy · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsABCB1, some ABCCs and SLCOs have been reported to affect the intracellular accumulation of various protease inhibitors in vitro and ex vivo. Darunavir is the most recently licensed protease inhibitor and we sought to investigate the ability of transport inhibitors to influence its intracellular accumulation in lymphocytes from healthy volunteers.
methodsThe intracellular accumulation of radiolabelled darunavir was assessed using CEM cells and ABCB1-overexpressing CEM(VBL) cells. Apical and basolateral transport of radiolabelled darunavir through MDCKII monolayers was also studied. Finally the ability of known inhibitors to influence intracellular accumulation of darunavir in peripheral blood mononuclear cells (PBMC) was investigated.
resultsCEM(VBL) cells (1.4 +/- 0.6, P < 0.001, 95% CI for the difference = 0.46, 0.80, n= 7) had significantly lower accumulation of darunavir compared with CEM cells (5.6 +/- 0.7, n= 7) and this was reversed by addition of tariquidar (30 nm, 4.6 +/- 0.8, P < 0.001, 95% CI =-0.64, -0.41, n= 4). In MDCKII-ABCBI cells, transport from the basal to the apical compartment was observed and this was also reversible with the addition of tariquidar. In PBMCs, dipyridamole (6.9 +/- 1.3, P < 0.01, 95% CI for the difference =-1.16, -0.30, (n= 8) significantly increased whilst montelukast (5.7 +/- 1.0, P < 0.01, 95% CI for the difference = 0.16, 0.79, n= 8) significantly decreased the intracellular accumulation of darunavir when compared with control (6.2 +/- 1.1, n= 8).
conclusionsDarunavir is a substrate for efflux and influx transporters in PBMC and intracellular concentrations can be manipulated using known inhibitors.
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