NDLI: Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model

Content Provider	Springer Nature Link
Author	Lewis, Andrew L. Holden, Rachel R. Chung, S. Ting Czuczman, Peter Kuchel, Timothy Finnie, John Porter, Susan Foster, David
Copyright Year	2012
Abstract	Irinotecan eluting embolization beads (DEBIRI) are currently being evaluated in the clinic for the treatment of colorectal cancer metastases to the liver. The aim of this study was to determine the safety and pharmacokinetics associated with two cycles of hepatic embolization using DEBIRI followed by intravenous administration of irinotecan. Pigs were embolized with DEBIRI (100–300 μm, 100 mg dose, n = 6) and blood samples taken over 24 h to determine plasma levels of irinotecan and SN-38 metabolite and for haematology and biochemistry. At 24 h an IV infusion of 250 mg/m$^{2}$ of irinotecan was administered and the plasma levels taken again. This cycle was repeated 3 weeks later. A single animal was subjected to a more aggressive regimen of embolization with 200 mg bead dose and IV of 350 mg/m$^{2}$ for two cycles. Three animals were sacrificed at 6 weeks and the remaining four (n = 3 standard dose, n = 1 high dose) animals at 12 weeks and detailed histopathology performed. All animals tolerated the treatments well, with only minor changes in haematological and biochemical parameters. There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks. Irinotecan plasma AUC values were similar in both the embolization and IV arms of the study. C$_{max}$ values obtained during the IV arms of the study are approximately double that of the embolization arms whilst T$_{max}$ times are shorter in the IV arms, supporting extended release of drug from the beads. Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route. No additive toxicity was observed as a consequence of the combined treatments. The combination of irinotecan delivery via drug eluting bead and IV was well-tolerated with no significant clinical effects. Pharmacokinetic analyses suggest the bioavailability from bead-based delivery of drug is double that of IV infusion, attributable to reduced drug clearance for the former.
Starting Page	115
Ending Page	127
Page Count	13
File Format	PDF
ISSN	09574530
Journal	Journal of Materials Science: Materials in Medicine
Volume Number	24
Issue Number	1
e-ISSN	15734838
Language	English
Publisher	Springer US
Publisher Date	2012-09-27
Publisher Place	Boston
Access Restriction	Subscribed
Subject Keyword	Biomaterials Polymer Sciences Ceramics, Glass, Composites, Natural Methods Metallic Materials Characterization and Evaluation of Materials Surfaces and Interfaces, Thin Films
Content Type	Text
Resource Type	Article
Subject	Biomaterials Biophysics Bioengineering Biomedical Engineering

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