---
title: "Protracted Intraventricular Infusion of Gemcitabine to Bypass the Blood–Brain Barrier"
id: "pubmed-42674692"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42674692"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42674692/"
doi: "10.21873/anticanres.18336"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Protracted Intraventricular Infusion of Gemcitabine to Bypass the Blood–Brain Barrier
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42674692
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42674692/)
- **DOI:** [10.21873/anticanres.18336](https://doi.org/10.21873%2Fanticanres.18336)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Background: The poor outcomes of brain tumors are partly due to the **blood-brain barrier** (BBB) limiting delivery of hydrophilic anticancer agents. Early animal work suggested that intracranial injection of hydrophilic dyes can bypass the BBB. - Objective: To test whether a protracted **intraventricular infusion** of the hydrophilic drug **gemcitabine** can circumvent the BBB and produce therapeutically relevant concentrations in brain tissue and cerebrospinal fluid (CSF). - Models and assays: Vital dye (Bleu Patente) distribution was compared after intracranial versus intravenous injection in guinea pigs, and after a 24 h intraventricular infusion in sheep. Gemcitabine levels were quantified by high-performance liquid chromatography. In vitro cytotoxicity was assessed in human glioblastoma cell lines (A172, U87-MG, U118-MG) using Crystal Violet after 72 h drug-free recovery. Tolerance of a single 24 h intraventricular infusion (20 mg) was evaluated in sheep. - Key pharmacokinetic findings: In guinea pigs, intracranial dye injection stained brain tissue while intravenous dye did not. In sheep, a 24 h intraventricular infusion produced deep cortical penetration of the dye. Brain concentrations of gemcitabine were higher after intracranial versus intravenous administration in guinea pigs. - Quantitative results in sheep: After a 24 h intraventricular infusion of 20 mg gemcitabine, mean concentrations measured were 1,415 µg/l in CSF and 850 µg/kg in brain tissue. - Pharmacodynamic relevance: These CSF and brain concentrations exceeded the reported IC90 values for the three tested human glioblastoma cell lines (A172, U87-MG, U118-MG) in vitro. - Safety/tolerance: A single 24 h intraventricular infusion of 20 mg gemcitabine was reported as well tolerated in sheep. - Mechanistic hypothesis: The authors propose that intraventricular delivery enables hydrophilic drugs to bypass the **BBB** by engaging the **glymphatic system**, allowing distribution from CSF into brain parenchyma. - Clinical implication: Given the high CSF and brain concentrations and acceptable tolerance in the animal model, the authors propose studying protracted intraventricular gemcitabine in patients with refractory primary or secondary brain tumors and meningeal metastasis. - Notes: Specific clinical dosing, long-term safety, efficacy outcomes in patients, and details of infusion protocols for humans were not reported in the source abstract.
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Affiliations Expand ### Affiliations * 1 Department of Onco-hematology, Centre Hospitalier, Saint Quentin, France; b.chauffert@ch-stquentin.fr. * 2 Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France; Galmiche.antoine@chu-amiens.fr. * 3 Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France. * 4 Department of Pharmacology and Toxicology, CHU Besançon, Besançon, France. * 5 Veterinary Clinic, Nuits Saint George, France. * 6 Department of Pathology, CHU Amiens, Amiens, France. * 7 Department of Neurosurgery, CHU Nancy, Nancy, France. * 8 Department of Ophthalmology, CHU Dijon, Dijon, France. * 9 Department of Pharmacy, Centre Hospitalier, Saint Quentin, France. * 10 Department of Oncology, CHU Amiens, Amiens, France. * 11 Department of Neurosurgery, CHU Dijon, Dijon, France. * PMID: **42674692** * DOI: [ 10.21873/anticanres.18336 ](https://doi.org/10.21873/anticanres.18336) Item in Clipboard # Protracted Intraventricular Infusion of Gemcitabine to Circumvent the Blood Brain Barrier Bruno Chauffert et al. Anticancer Res. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Anticancer Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anticancer+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Anticancer+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42674692/) . 2026 Sep;46(9):4827-4840. doi: 10.21873/anticanres.18336. ### Authors [Bruno Chauffert](https://pubmed.ncbi.nlm.nih.gov/?term=Chauffert+B&cauthor_id=42674692)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-1 "Department of Onco-hematology, Centre Hospitalier, Saint Quentin, France; b.chauffert@ch-stquentin.fr."), [Antoine Galmiche](https://pubmed.ncbi.nlm.nih.gov/?term=Galmiche+A&cauthor_id=42674692)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-2 "Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France; Galmiche.antoine@chu-amiens.fr."), [Christophe Louandre](https://pubmed.ncbi.nlm.nih.gov/?term=Louandre+C&cauthor_id=42674692)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-3 "Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France."), [Bernard Royer](https://pubmed.ncbi.nlm.nih.gov/?term=Royer+B&cauthor_id=42674692)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-4 "Department of Pharmacology and Toxicology, CHU Besançon, Besançon, France."), [Michel Simonet](https://pubmed.ncbi.nlm.nih.gov/?term=Simonet+M&cauthor_id=42674692)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-5 "Veterinary Clinic, Nuits Saint George, France."), [Nelly Guilain](https://pubmed.ncbi.nlm.nih.gov/?term=Guilain+N&cauthor_id=42674692)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-6 "Department of Pathology, CHU Amiens, Amiens, France."), [Fabien Rech](https://pubmed.ncbi.nlm.nih.gov/?term=Rech+F&cauthor_id=42674692)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-7 "Department of Neurosurgery, CHU Nancy, Nancy, France."), [Pierre Simonet](https://pubmed.ncbi.nlm.nih.gov/?term=Simonet+P&cauthor_id=42674692)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-5 "Veterinary Clinic, Nuits Saint George, France."), [Maxime Sibert](https://pubmed.ncbi.nlm.nih.gov/?term=Sibert+M&cauthor_id=42674692)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-8 "Department of Ophthalmology, CHU Dijon, Dijon, France."), [Ahmed Abdaoui](https://pubmed.ncbi.nlm.nih.gov/?term=Abdaoui+A&cauthor_id=42674692)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-9 "Department of Pharmacy, Centre Hospitalier, Saint Quentin, France."), [Alexandre Cau](https://pubmed.ncbi.nlm.nih.gov/?term=Cau+A&cauthor_id=42674692)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-9 "Department of Pharmacy, Centre Hospitalier, Saint Quentin, France."), [Mathieu Boone](https://pubmed.ncbi.nlm.nih.gov/?term=Boone+M&cauthor_id=42674692)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-10 "Department of Oncology, CHU Amiens, Amiens, France."), [Jacques Beaurain](https://pubmed.ncbi.nlm.nih.gov/?term=Beaurain+J&cauthor_id=42674692)[ 11 ](https://pubmed.ncbi.nlm.nih.gov/42674692/#short-view-affiliation-11 "Department of Neurosurgery, CHU Dijon, Dijon, France.") ### Affiliations * 1 Department of Onco-hematology, Centre Hospitalier, Saint Quentin, France; b.chauffert@ch-stquentin.fr. * 2 Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France; Galmiche.antoine@chu-amiens.fr. * 3 Department of Biochemistry, CHU Amiens, UR7516 UPJV, Amiens, France. * 4 Department of Pharmacology and Toxicology, CHU Besançon, Besançon, France. * 5 Veterinary Clinic, Nuits Saint George, France. * 6 Department of Pathology, CHU Amiens, Amiens, France. * 7 Department of Neurosurgery, CHU Nancy, Nancy, France. * 8 Department of Ophthalmology, CHU Dijon, Dijon, France. * 9 Department of Pharmacy, Centre Hospitalier, Saint Quentin, France. * 10 Department of Oncology, CHU Amiens, Amiens, France. * 11 Department of Neurosurgery, CHU Dijon, Dijon, France. * PMID: **42674692** * DOI: [ 10.21873/anticanres.18336 ](https://doi.org/10.21873/anticanres.18336) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background/aim:** Poor prognosis of brain tumors is partly related to the blood brain barrier (BBB) to hydrophilic anticancer drugs. Early studies demonstrated that intracranial injection of vital dyes bypassed BBB in cats. We investigated if intraventricular infusion of gemcitabine can circumvent the blood-brain barrier and achieve therapeutically relevant drug concentrations within the brain and cerebrospinal fluid. **Materials and methods:** Brain diffusion of the vital hydrophilic Bleu Patente dye was studied after intracranial or intravenous injection in guinea pig, or after a 24 h protracted intraventricular infusion in sheep. Gemcitabine, a hydrophilic anticancer drug, was quantified by high-performance liquid chromatography. Viability of human glioblastoma cells was studied _in vitro_. Cells were maintained in drug-free fresh culture medium for 72 h after drug exposure before an assay with Crystal Violet. Tolerance of a single 24 h intraventricular infusion of gemcitabine was evaluated in sheep. **Results:** Bleu Patente diffused into brain of guinea pigs after an intracranial injection, whereas brain remained unstained after an intravenous administration. After a 24 h intraventricular infusion, dye penetrated deeply into the cerebral cortex of sheep. Brain concentration of gemcitabine was higher following intracranial injection than after intravenous administration in guinea pigs. At the end of a 24 h intraventricular infusion of 20 mg gemcitabine in sheep, mean concentrations reached 1,415 microg/l in cerebrospinal fluid and 850 microg/kg in brain. These concentrations exceeded the IC90 values of gemcitabine for A172, U87-MG, and U118-MG human glioblastoma cell lines. Tolerance of a single 24 h intraventricular infusion of 20 mg gemcitabine was good in sheep. **Conclusion:** We hypothesize that intraventricular injections allow the hydrophilic drugs to circumvent BBB by using the glymphatic system. Given high concentrations in the cerebrospinal fluid and brain, and given its good tolerability, we propose to study protracted intraventricular infusion of gemcitabine in patients with refractory primary, secondary brain tumors, and meningeal metastasis. **Keywords:** Gemcitabine; blood-brain barrier; glioblastoma; glymphatic system; intraventricular infusion; meningeal metastasis. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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