K-3398a. Local Tissue and Intravascular Safety Evaluation of a 5-Fluorouracil Coated Central Venous Catheter in a Goat Model
Session: Poster Session: Catheter-Related Bloodstream Infections
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: A recent, large, randomized clinical trial of a novel 5-Fluorouracil (5-FU) coated central venous catheter (CVC) demonstrated the efficacy and clinical safety of a 5-FU-coated CVC. During preclinical development of the CVC, the local tissue and vasculature reactivity as well as 5-FU plasma levels were examined in a large animal model which closely mimics the clinical use of this novel 5-FU-coated anti-infective CVC. Methods: 5-FU-coated CVCs and uncoated control CVCs were inserted into the jugular veins of goats following clinical protocols for CVC insertion and left in place for either 14 or 21 days (N=8 per group). At each final endpoint, both macroscopic and microscopic evaluations were performed at the catheter/host tissue interfaces and vessel contact points. Plasma samples from goats receiving drug loaded CVC were analyzed for 5-FU using liquid chromatography/tandem mass spectrometry on days 0,1,3,7,14 and 21 (for the second group only) with a lower limit of quantitation of 1 ng/mL. In addition, explanted 5-FU loaded CVCs were analyzed for residual drug content. Results: Histopathology and macroscopic evaluation showed the 5-FU loaded CVC produced no greater response than the control catheters. No detectable level of 5-FU was present in any of the plasma samples. The average retained amounts of 5-FU from the explanted CVCs after 14 and 21-day in vivo implantation were 14.4% and 7.8% of the original loaded amount, respectively. These data were consistent with the in vitro release profile of 5-FU from the CVC. Conclusions: The results of this study indicate that gradual release of 5-FU from the drug loaded CVC occurs in vivo for up to 21 days without detectable systemic exposure or local tissue toxicity.
Alexandra Chamberlain, PhD, Angiotech Pharmaceuticals, Inc., Scott Rosebrough, PhD, Angiotech Pharmaceuticals, Inc., Henrietta, NY and  S. F. Rosebrough,
Angiotech Pharmaceuticals, Inc. Role(s): Employee, Received: Salary.