Basic Science: Reconstruction

Moderated Poster Session

MP3-12 - Tissue and Pharmacokinetic Response to Treatment with a Drug-Coated Balloon in a Canine Urethra Model

Presenting Author(s)

• 

  Ramón Virasoro, MD

  Associate Professor
  Eastern Virginia Medical School

Author(s)

• PB

  Peter Barnett

  R&D Manager
  Urotronic
• SR

  Serge Rousselle

  DMV, ACVPV

Introduction & Objective : Drug Coated Balloons (DCBs) utilizing paclitaxel have emerged as a potential therapeutic alternative in the treatment of urethral stricture disease. This study was designed to gather data concerning; pharmacokinetics, overlapping treatments, dosing, and safety for drug-coated balloon (DCB) treatments in the urethra of healthy canine mongrels

Methods : The preclinical animal study had 3 arms.  The first arm, a non-overlapping dose arm, treated 29 research bred canine mongrels with two non-overlapping treatments, resulting in each canine mongrel receiving a total of 5.278 mg of paclitaxel. The second arm, a double overlapping dose arm, treated 12 research bred canine mongrels at three sites in the anterior urethra with two overlapping DCB treatments. Each mongrel was dosed with a total of 6 DCBs giving a total paclitaxel dose of 15.834 mg. In the final, control arm, 6 research bred canine mongrels received three non-overlapping non-coated balloon catheters in their anterior urethra.

Results : In every case, no treatment failures were reported, and the mortality rate in the study was 0% (0/47). H&E stained tissue samples showed hypocellularity in the sub-urothelium mucosa in both DCB treatment arms. The urothelium was completely healed with normal cellularity at 28 days for the non-overlapping dose arm and was completely healed with normal cellularity at 70 days for the double overlapping dose arm. The amount of drug in the double overlapped dosed canines was approximately twice the standard dose.  Paclitaxel was quantified in all urethral tissue samples from 1 hour through 28 days. Paclitaxel remained quantifiable at 70 days for 75% of the samples. For the standard dose urethral tissue treatment sites T_maxwas 1 hour with a C_maxof 71.3 µg/g.  The paclitaxel level in off-target tissues was highest at 1 hour but was 1000 times lower than the urethral tissue treatment sites.  Almost all the off-target tissue samples were below the limit of quantification at 7 days, and all the samples were below the limit of quantification at 28 days.

Conclusions :

The findings indicate no device-associated or drug related adverse reactions have been identified for both non-overlapping dosing and double overlapping dosing in the urethra.  Paclitaxel can be successfully delivered to the urethra tissue with sustained elevated drug levels exceeding 28 days and the drug resides at low but quantifiable levels exceeding 70 days.