Category: Basic Science: Reconstruction
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 Tmaxwas 1 hour with a Cmaxof 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.
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.
Eastern Virginia Medical School
Dr. Ramón Virasoro earned his medical degree from the University of Buenos Aires, Argentina, in 1991. He completed both general surgery and urology residencies at Centro de Educación Médica e Investigaciones Clínicas (CEMIC) in Buenos Aires, Argentina from 1992 to 1999. He practiced general urology from 2000-2004 at CEMIC, where he was a member of the kidney transplant team.
Dr. Virasoro completed his fellowship in Adult and Pediatric Genitourinary Reconstructive Surgery in 2007, in Norfolk, VA.
Back in Argentina, he developed the genitourinary reconstructive surgery section at CEMIC. He was the coordinator until he joined Urology of Virginia, in 2011.
Dr. Virasoro is a member of the American Urological Association, and served as the Argentine representative for the International Members Committee of the AUA from 2008 to 2011. He is also an active member of the Society of Genitourinary Reconstructive Surgeons (GURS), and The Société Internationale d’Urologie (SIU).
Dr. Virasoro is a board member of GURS and Board memeber and International Medical Educator (IME) with Physicians for Peace, a local non-profit organization. Since 2013, he has completed bi-annual humanitarian missions to the Dominican Republic (DR), where he performs reconstructive surgeries for indigent patients.
Dr. Virasoro is the Co-Founder, and Co-Director of a Genitourinary Reconstructive Surgery Fellowship in Santo Domingo, DR. The fellowship, accredited by Universidad Autónoma de Santo Domingo, est. 1538, will train three local Urologists over the next 5 years.
Dr. Virasoro has published several articles regarding genitourinary reconstruction, and has authored many chapters in urology. He has presented his research at numerous national and international meetings.
When not working, Dr. Virasoro enjoys time with his family.