ArticleBiological & pharmaceutical bulletin2009
P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines.
Article in Biological & pharmaceutical bulletin, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 66 citations in OpenAlex.
- Investigating how HIV-1 antiretrovirals differentially behave as substrates and inhibitors of P-glycoprotein via molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- Plasma Concentrations of Rosmarinic Acid in Patients on Antiretroviral Therapy: In Silico Exploration Based on Clinical Data.International journal of molecular sciences · 2024Article
- Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities.Viruses · 2023Review
- A Unique In Vitro Assay to Investigate ABCB4 Transport Function.International journal of molecular sciences · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Evaluation of the Potency of Anti-HIV and Anti-HCV Drugs to Inhibit P-Glycoprotein Mediated Efflux of Digoxin in Caco-2 Cell Line and Human Precision-Cut Intestinal Slices.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Knockout of ABC transporters by CRISPR/Cas9 contributes to reliable and accurate transporter substrate identification for drug discovery.Frontiers in pharmacology · 2022Article
- Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines.Scientific reports · 2021Article
- Incorporation of docosahexaenoic acid (DHA) enhances nanodelivery of antiretroviral across the blood-brain barrier for treatment of HIV reservoir in brain.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Potential Tools for Eradicating HIV Reservoirs in the Brain: Development of Trojan Horse Prodrugs for the Inhibition of P-Glycoprotein with Anti-HIV-1 Activity.Journal of medicinal chemistry · 2020Article
- Article
- Current pharmacotherapy for the treatment of dyslipidemia associated with HIV infection.Expert opinion on pharmacotherapy · 2019Review
- Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives.Frontiers in physiology · 2018Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Interaction of Rifampin and Darunavir-Ritonavir or Darunavir-CobicistatAntimicrobial agents and chemotherapy · 2017Article
- Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir.BioMed research international · 2017Article
- Cerebrospinal fluid concentrations of tenofovir and emtricitabine in the setting of HIV-1 protease inhibitor-based regimens.Journal of clinical pharmacology · 2016Article
- Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy.Clinical pharmacokinetics · 2016Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Darunavir (DRV) is a nonpeptidic protease inhibitor (PI) approved for the treatment of human immunodeficiency virus (HIV) infection. DRV displays potent activity against HIV strains resistant to other available PIs. Coadministration with ritonavir (RTV) improves the oral bioavailability of DRV. Inhibition of cytochrome P450 by RTV has been proposed as a mechanism for enhanced DRV bioavailability. However, interaction of these drugs with intestinal transporters has not been elucidated. This study was performed to explore the involvement of P-glycoprotein in transcellular DRV transport in monolayers of human intestinal Caco-2 and in ABCB1 multidrug resistance 1, (MDR1) gene-transfected renal LLC-PK1 (L-MDR1) cell lines. Transepithelial transport of DRV in Caco-2 cell monolayers was 2-fold greater in the basal-to-apical direction compared to that in the opposite direction. RTV had a significant inhibitory effect on the efflux transport of DRV in Caco-2 cells. The apical-to-basal DRV transport was enhanced by P-glycoprotein inhibitors, cyclosporin A and verapamil, as well as multidrug resistance-related protein (MRP/ABCC) inhibitors, probenecid and MK571. Using the L-MDR1 cell line, basal-to-apical DRV transport was much greater than in the opposite direction. Furthermore, cyclosporin A markedly inhibited the basal-to-apical DRV transport. RTV significantly increased the apical-to-basal transport of DRV in L-MDR1 cells, but reduced transport in the opposite direction. DRV inhibited P-glycoprotein-mediated efflux of calcein-acetoxymethyl ester in L-MDR1 cells with the inhibitory potency of 121 microM. These findings suggest that DRV is a substrate of P-glycoprotein and MRP, most likely MRP2. RTV appeared to inhibit P-glycoprotein, thereby enhancing the absorptive transport of DRV.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.