gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Calculation of spatial distribution of intracerebral drug delivery

Berechnung der räumlichen Verteilung intrazerebral applizierter Pharmazeutika

Meeting Abstract

  • corresponding author Friedrich Weber - Klinik für Neurochirurgie, Klinikum Saarbrücken, Saarbrücken
  • A. Hartlep - BrainLab, Heimstetten
  • M. Brady - BrainLab, Heimstetten
  • R. Raghavan - BrainLab, Heimstetten
  • C. Pedain - BrainLab, Heimstetten

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocDI.07.07

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0218.shtml

Veröffentlicht: 23. April 2004

© 2004 Weber et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Convection enhanced delivery (CED) is currently being used in a number of clinical trials. The drug is delivered to the brain using a pressure gradient along with the diffusive forces resulting from a concentration gradient. The BBB is circumvented by locally placing a catheter into the brain.

Methods

Five patients with radiologically evident recurrent glioblastoma, who did not have chemotherapy within four weeks before treatment, and did never receive systemic Taxol therapy, were enrolled in this study. Histological evidence of tumour recurrence was obtained before treatment. Up to three catheters were stereotactically placed in each patient. We used a pediatric ventricular catheter model, from which the tip was cut off to turn it into an end port catheter. Outer diameter of the catheter is 2.1mm. All catheters were tunnelled and secured multiple times. A CT scan was obtained to confirm catheter placement. Infusion was subsequently started at the ward. The infusions were conducted using one standard syringe pump per catheter. To assess effectiveness of the physical drug distribution from the selected catheter trajectories, we infused Gadolinium DTPA in a concentration of 1mMol/ml for 48 hours with a flow rate of 10 microL per minute. The distribution of the contrast agent was obtained by taking T1 weighted MRI scans at 12, 24, and 48 hours. After 48 hours, the infusion of contrast agent was stopped, and the syringes containing the diluted contrast agent were replaced with syringes containing Taxol diluted in cremophore. The total dose of Taxol was 3.6mg in 24 hours. Thus, a total dose of 14.4mg of Taxol was administered over the 96-hour infusion.

Results

The intracerebral delivery of Gadolineum DTPA was well tolerated in all five patients. The spatial distribution of the contrast medium revealed valuable information about the volumes of distribution that can be expected from the catheters. Taxol infusion was well tolerated and an anti tumour effect was visible at follow-up scans.

Conclusions

Local administration of Gadolinium DTPA into the brain is a promising pathway towards assessing fluid distribution in convection-enhanced delivery. Intracerebral CED of Taxol was safe and showed promising effects.