Rami Tzafriri; Brett Zani; Steve Alston; Elazer Edelman. ‘Multiple drug coated balloon exposures increase arterial permeability and drug retention.’
Poster presented at: Transcatheter Cardiovascular Therapeutics (TCT), Oct 25-Nov 2, 2016, Washington, DC.
Summary: It is thought that increased dose or number of drug-coated balloon (DCB) inflations increases drug delivery and tissue retention – this however has never been validated and this we examined. Paclitaxel (PTX) coated balloons (W.L. Gore, Flagstaff AZ) with 4.1 (5×40 mm) or 3.6 μg/mm2 (6×40 mm) PTX were inflated for 60 sec once or three DCB sequentially at the same angiographic site in 30 Yorkshire swine peripheral arteries.
While ∼75% of the PTX load was released from the balloons independent of the number of inflations per artery, the amount deposited in the wall and retained over time differed. Arteries in the clinical single dose group absorbed only 72.1±0.6 μg PTX, of which 97% was cleared with a half-life of 8 hours. Surprisingly, three exposures produced 6.6-fold more PTX, twice the difference from dose alone (478±8.1 μg, p<0.0001) and what was deposited was cleared slower; 92% with a half-life of 13 hours (p=0.0028).
In conclusion, tissue retention from DCB benefits from repeat inflations but NOT due to increased dose exposure – suggesting that repeated dilation may prepare the artery for enhanced absorption and/or overcome restrictions of single dose retention. These studies beg further evaluation in disease models and reevaluation of clinical use protocols for DCB.