ArticleAntimicrobial agents and chemotherapy2014
Role of P-glycoprotein in the distribution of the HIV protease inhibitor atazanavir in the brain and male genital tract.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Contemporary antiretroviral pharmacology in the male genital tract: implications for HIV treatment and prevention.Antimicrobial agents and chemotherapy · 2026Review
- Intracellular Penetration of Atazanavir, Ritonavir and Dolutegravir With Concomitant Rifampicin: A Dose Escalation Study.Clinical pharmacology and therapeutics · 2025Article
- Testis Is a Sanctuary Site for HIV-1.Advances in experimental medicine and biology · 2025Review
- Intranasal Administration of Dolutegravir-Loaded Nanoemulsion-Based In Situ Gel for Enhanced Bioavailability and Direct Brain Targeting.Gels (Basel, Switzerland) · 2023Article
- Drug transport across the blood-testis barrier.American journal of translational research · 2022Review
- Nanoparticle delivery system, highly active antiretroviral therapy, and testicular morphology: The role of stereology.Pharmacology research & perspectives · 2021Review
- Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy.AAPS PharmSciTech · 2021Article
- Cerebral Vascular Toxicity of Antiretroviral Therapy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- An update on drug-drug interactions between antiretroviral therapies and drugs of abuse in HIV systems.Expert opinion on drug metabolism & toxicology · 2020Review
- Opioid Use Disorders in People Living with HIV/AIDS: A Review of Implications for Patient Outcomes, Drug Interactions, and Neurocognitive Disorders.Pharmacy (Basel, Switzerland) · 2020Article
- Automated synthesis, preclinical toxicity, and radiation dosimetry of [EJNMMI research · 2020Article
- P-Glycoprotein-Mediated Efflux Reduces the In Vivo Efficacy of a Therapeutic Targeting the Gastrointestinal Parasite Cryptosporidium.The Journal of infectious diseases · 2019Article
- Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Review
- Neuroimmune Axes of the Blood-Brain Barriers and Blood-Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions.Pharmacological reviews · 2018Review
- Signaling pathways regulating blood-tissue barriers - Lesson from the testis.Biochimica et biophysica acta. Biomembranes · 2018Review
- Therapeutic Potential and Utility of Elacridar with Respect to P-glycoprotein Inhibition: An Insight from the Published In Vitro, Preclinical and Clinical Studies.European journal of drug metabolism and pharmacokinetics · 2017Review
- HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities.AIDS research and human retroviruses · 2017Review
- Nanoformulated Antiretrovirals for Penetration of the Central Nervous System: State of the Art.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Exploring the anatomical HIV reservoirs: role of the testicular tissue.AIDS (London, England) · 2016Article
- Semen as the Way Forward to Understand HIV-1 Transmission.The Journal of infectious diseases · 2016Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-testis barrier and blood-brain barrier are responsible for protecting the male genital tract and central nervous system from xenobiotic exposure. In HIV-infected patients, low concentrations of antiretroviral drugs in cerebrospinal fluid and seminal fluid have been reported. One mechanism that may contribute to reduced concentrations is the expression of ATP-binding cassette drug efflux transporters, such as P-glycoprotein (P-gp). The objective of this study was to investigate in vivo the tissue distribution of the HIV protease inhibitor atazanavir in wild-type (WT) mice, P-gp/breast cancer resistance protein (Bcrp)-knockout (Mdr1a-/-, Mdr1b-/-, and Abcg2-/- triple-knockout [TKO]) mice, and Cyp3a-/- (Cyp) mice. WT mice and Cyp mice were pretreated with a P-gp/Bcrp inhibitor, elacridar (5 mg/kg of body weight), and the HIV protease inhibitor and boosting agent ritonavir (2 mg/kg intravenously [i.v.]), respectively. Atazanavir (10 mg/kg) was administered i.v. Atazanavir concentrations in plasma (Cplasma), brain (Cbrain), and testes (Ctestes) were quantified at various times by liquid chromatography-tandem mass spectrometry. In TKO mice, we demonstrated a significant increase in atazanavir Cbrain/Cplasma (5.4-fold) and Ctestes/Cplasma (4.6-fold) ratios compared to those in WT mice (P<0.05). Elacridar-treated WT mice showed a significant increase in atazanavir Cbrain/Cplasma (12.3-fold) and Ctestes/Cplasma (13.5-fold) ratios compared to those in vehicle-treated WT mice. In Cyp mice pretreated with ritonavir, significant (P<0.05) increases in atazanavir Cbrain/Cplasma (1.8-fold) and Ctestes/Cplasma (9.5-fold) ratios compared to those in vehicle-treated WT mice were observed. These data suggest that drug efflux transporters, i.e., P-gp, are involved in limiting the ability of atazanavir to permeate the rodent brain and genital tract. Since these transporters are known to be expressed in humans, they could contribute to the low cerebrospinal and seminal fluid antiretroviral concentrations reported in the clinic.
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