Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood–Brain Barrier Opening
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Le résumé fourni par la source
PURPOSE: The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug retention following short-lived BBB opening is unknown. We investigated the effect of LIPU/MB on the concentration of carboplatin and fluorescein over time and compared the parenchymal retention of temozolomide (TMZ), carboplatin, and fluorescein in the nonsonicated brain. EXPERIMENTAL DESIGN: We analyzed four patients who underwent intraoperative LIPU/MB with intravenous administration of carboplatin and fluorescein in the NCT04528680 clinical trial. Microdialysis catheters were implanted into sonicated and nonsonicated brain regions, and drug levels were measured over 24 hours. Published microdialysis data of TMZ without LIPU/MB were used for comparison. RESULTS: LIPU/MB led to sustained elevated parenchymal drug concentrations, achieving a 3.1-fold increase in brain-to-plasma AUC for carboplatin and fluorescein (P = 0.03). In the nonsonicated brain, TMZ concentrations remained below their plasma levels, as parenchymal drug clearance mirrored plasma clearance. In contrast, BBB-impermeable drugs such as carboplatin and fluorescein exhibited delayed parenchymal clearance, resulting in higher brain than plasma drug levels over time. Parenchymal drug clearance of carboplatin and fluorescein was not affected by sonication. CONCLUSIONS: Following LIPU/MB, BBB-impermeable drugs exhibit sustained elevated parenchymal concentrations surpassing their plasma levels, highlighting the bidirectional restriction of drug passage by the BBB. Future studies are warranted to explore drug trapping and the efficacy of sustained exposure to cytotoxic drugs for the treatment of brain-infiltrating tumors.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood–Brain Barrier Opening
- Date Crossref
- 10/06/2025
- Éditeur
- American Association for Cancer Research (AACR)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Northwestern University pays non établi dans la noticeUniversité ou école supérieure
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Robert H. Lurie Comprehensive Cancer Center of Northwestern University pays non établi dans la noticeÉtablissement de santé
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City of Hope pays non établi dans la noticeÉtablissement de santé
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Beckman Research Institute pays non établi dans la noticeStructure de recherche
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Feinberg School of Medicine Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Lyon pays non établi dans la noticeInstitution
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Carthera pays non établi dans la noticeInstitution
Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University et City of Hope, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.