All Blood Brain Barrier Cell Types Demonstrate Capability to Influence Differential Tenofovir and Emtricitabine Metabolism and Transport in the Brain DOI Creative Commons
Hannah Wilkins,

Stephen Knerler,

Ahmed Warshanna

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(11), P. 3626 - 3640

Published: Oct. 18, 2024

The blood brain barrier (BBB) represents a significant obstacle in drug penetration that challenges efforts the treatment of neurological disorders. Therapeutically targeting requires interactions with each BBB cell type, including endothelial cells, pericytes, and astrocytes. Yet, relative contribution these types to mechanisms facilitate disposition is not well characterized. Here, we use first-line antiretroviral therapies, tenofovir (TFV) emtricitabine (FTC), as models investigate transport metabolism at may influence access brain. We evaluated regional cell-type-specific using rhesus macaques vitro primary human cells. report heterogeneous distribution TFV, FTC, their active metabolites, which cerebrospinal fluid measures could reflect. found all possessed functional drug-metabolizing enzymes transporters promoted TFV FTC uptake pharmacologic activation. Pericytes astrocytes emerged pharmacologically dynamic cells rival hepatocytes were uniquely susceptible modulation by disease treatment. Together, our findings demonstrate importance considering unique entity rather than viewing it an extension liver, type possesses distinct capacities contribute differential disposition. Further, work highlights pathways regulate impact therapeutic alleviate neurologic disease.

Language: Английский

Monitoring HIV Antiretroviral Therapy via Aptamer‐Based Measurements in Preclinical Animal Models, in Human Plasma DOI Creative Commons
Jing Li, Vincent Clark, Chen‐Hsu Yu

et al.

Advanced Sensor Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract Monitoring the concentration of antiretroviral drugs is critical to ensuring patient adherence HIV treatment and prevention regimens, which crucial for drug efficacy. These tools may also be useful screening samples at blood donation centers avert potential new infections. The current benchmark method support monitoring, liquid chromatography coupled mass spectrometry (LC‐MS), requires centralized facilities with costly instrumentation, has blood‐to‐result turnaround times days weeks, making it impractical effective monitoring. Seeking overcome this issue, an aptamer developed emtricitabine, present in most combination therapies market used both infection management prevention. clinically relevant sensitivity biofluids highly selective relative close analogs such as cytosine, cytidine, fluorocytidine, lamivudine (a.k.a. 3TC). Using aptamer, two analytical assays are developed, one continuous, in‐vivo emtricitabine monitoring rodent research models, rapid high‐throughput levels human plasma. Through blinded validation, clinical assay achieved 86.9% positive 100% negative correlation, overall agreement rate 95% LC‐MS method.

Language: Английский

Citations

0
Cannabis use is associated with a lower likelihood of presence of HIV drug resistance mutations in a retrospective cohort of adults with HIV DOI
Jonathan F. Hale,

S.J Reynolds,

Heather R. Kates

et al.

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2025, Volume and Issue: 4(1), P. 49 - 57

Published: Feb. 7, 2025

A significant clinical concern in the era of Pre-Exposure Prophylaxis (PrEP) is increased incidence HIV Anti-Retroviral Drug Resistance Mutations (ARV-DRM). Previous research has indicated that there an association between substance use and failed viral suppression, which can lead to ARV-DRM. The goal this retrospective study was investigate whether as determined by at least one positive urinalysis screen associated with increased/decreased odds having a This used firth logistic regression analyses data retrieved from National NeuroAIDS Tissue Consortium Data Coordinating Center examine relationship dataset analyzed 614 participants following criteria: HIV+ status, paired plasma cerebrospinal fluid (CSF) load measurement, use, 18 years age, analysis DRM CSF/Plasma. Cannabis predictor ARV-DRM lower (odds ratio=0.189), after accounting for demographic variables interaction polysubstance cannabis use. negative observed test high viremia (>1,000 copies/mL) but not CSF Escape (viral CSF>viral plasma). above results may suggest immunomodulatory role impacts propensity These findings could incentivize future further effects on development

Language: Английский

Citations

0
Pharmacokinetics–Pharmacodynamics Modeling for Evaluating Drug–Drug Interactions in Polypharmacy: Development and Challenges DOI
Di Zhao, Ping Huang, Li Yu

et al.

Clinical Pharmacokinetics, Journal Year: 2024, Volume and Issue: 63(7), P. 919 - 944

Published: June 18, 2024

Language: Английский

Citations

2
Blood–Brain Barrier Permeability is Affected by Changes in Tight Junction Protein Expression at High-Altitude Hypoxic Conditions—this may have Implications for Brain Drug Transport DOI
Guiqin Liu, Qian Wang,

Tian Lu

et al.

The AAPS Journal, Journal Year: 2024, Volume and Issue: 26(5)

Published: Aug. 6, 2024

Language: Английский

Citations

1
Drug Metabolism and Transport Capacity of Endothelial Cells, Pericytes, and Astrocytes: Implications for CNS Drug Disposition DOI Creative Commons
Hannah Wilkins,

Stephen Knerler,

Ahmed Warshanna

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Summary Therapeutically targeting the brain requires interactions with endothelial cells, pericytes, and astrocytes at blood barrier (BBB). We evaluated regional cell-type specific drug metabolism transport mechanisms using rhesus macaques in vitro treatment of primary human cells. Here, we report heterogenous distribution representative drugs, tenofovir (TFV), emtricitabine (FTC), their active metabolites, which cerebrospinal fluid measures could not reflect. found that all BBB cell types possessed functional metabolizing enzymes transporters promoted TFV FTC uptake pharmacologic activation. Pericytes emerged as pharmacologically dynamic cells rivaled hepatocytes were uniquely susceptible to modulation by disease treatment. Together, our findings demonstrate importance considering a unique entity, rather than viewing it an extension liver, each type possesses distinct capacities contribute differential disposition.

Language: Английский

Citations

0
All Blood Brain Barrier Cell Types Demonstrate Capability to Influence Differential Tenofovir and Emtricitabine Metabolism and Transport in the Brain DOI Creative Commons
Hannah Wilkins,

Stephen Knerler,

Ahmed Warshanna

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(11), P. 3626 - 3640

Published: Oct. 18, 2024

The blood brain barrier (BBB) represents a significant obstacle in drug penetration that challenges efforts the treatment of neurological disorders. Therapeutically targeting requires interactions with each BBB cell type, including endothelial cells, pericytes, and astrocytes. Yet, relative contribution these types to mechanisms facilitate disposition is not well characterized. Here, we use first-line antiretroviral therapies, tenofovir (TFV) emtricitabine (FTC), as models investigate transport metabolism at may influence access brain. We evaluated regional cell-type-specific using rhesus macaques vitro primary human cells. report heterogeneous distribution TFV, FTC, their active metabolites, which cerebrospinal fluid measures could reflect. found all possessed functional drug-metabolizing enzymes transporters promoted TFV FTC uptake pharmacologic activation. Pericytes astrocytes emerged pharmacologically dynamic cells rival hepatocytes were uniquely susceptible modulation by disease treatment. Together, our findings demonstrate importance considering unique entity rather than viewing it an extension liver, type possesses distinct capacities contribute differential disposition. Further, work highlights pathways regulate impact therapeutic alleviate neurologic disease.

Language: Английский

Citations

0