ArticleThe Journal of antimicrobial chemotherapy2010
Concentration-dependent effects and intracellular accumulation of HIV protease inhibitors in cultured CD4 T cells and primary human lymphocytes.
Article in The Journal of antimicrobial chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 1: Model for the Free-Drug Mixture.Journal of pharmaceutical sciences · 2022Article
- Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Influence of drug transport proteins on the pharmacokinetics and drug interactions of HIV protease inhibitors.Journal of pharmaceutical sciences · 2011Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe intracellular and plasma concentrations of HIV protease inhibitors (HPIs) vary widely in vivo. It is unclear whether there is a concentration-dependent effect of HPIs such that at increasing concentration they may either block their own efflux (leading to 'autoboosting') or influx (leading to saturability/decreased intracellular accumulation).
methodThe effects of various concentrations (0-30 microM) of lopinavir, saquinavir, ritonavir and atazanavir on the accumulation of [(14)C]lopinavir, [(3)H]saquinavir, [(3)H]ritonavir and [(3)H]atazanavir, respectively, were investigated in CEM(parental), CEM(VBL) [P-glycoprotein (ABCB1) overexpressing], CEM(E1000) (MRP1 overexpressing) and in peripheral blood mononuclear cells (PBMCs). We also investigated the effects of inhibitors of ABCB1/ABCG2 (tariquidar), ABCC (MK571) and ABCC1/2 (frusemide), singly and in combination with HPIs, on cellular accumulation.
resultsIn all the cell lines, with increasing concentration of lopinavir, saquinavir and ritonavir, there was a significant increase in the cellular accumulation of [(14)C]lopinavir, [(3)H]saquinavir and [(3)H]ritonavir. Tariquidar, MK571 and frusemide (alone and in combination with lopinavir, saquinavir and ritonavir) significantly increased the accumulation of [(14)C]lopinavir, [(3)H]saquinavir and [(3)H]ritonavir. Ritonavir (alone or in combination with tariquidar) decreased the intracellular accumulation of [(3)H]ritonavir in PBMCs. Atazanavir decreased the accumulation of [(3)H]atazanavir in a concentration-dependent manner in all of the cells tested.
conclusionsThere are complex and variable drug-specific rather than class-specific effects of the HPIs on their own accumulation.
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