Pharmacokinetic Study of Paclitaxel Concentration after Drug-Eluting Balloon Angioplasty in the Iliac Artery of Healthy and Atherosclerotic Rabbit Models

Abstract

PurposeTo assess whether the presence of an atherosclerotic lesion may alter the deposition kinetics of paclitaxel on the arterial wall after drug-eluting balloon (DEB) angioplasty, as well as paclitaxel concentrations in serum and in the recovered balloons. Materials and MethodsThree New Zealand White rabbit models were created: an atheroma group (arterial mechanical injury and hyperlipidic diet; group A), a prelesional group (fat arterial infiltration, hyperlipidic diet; group B), and a control healthy group (group C). Forty-five animals underwent DEB angioplasty in the iliac artery. Arteries and serum samples were analyzed by liquid chromatography/tandem mass spectrometry at 1, 24, 48, 72, and 96 hours (arteries) and at 1, 6, 12, and 24 hours (serum). Recovered balloons were analyzed by UV chromatography. Histologic and statistical analyses were also performed. ResultsGroup A showed significantly higher arterial paclitaxel concentrations in the first hour after DEB angioplasty (632.05 ng/mg ± 125.75 in group A vs 179.55 ng/mg ± 45.64 and 168.54 ng/mg ± 83.48 in groups B and C, respectively; P < .05). Paclitaxel was undetectable in serum at 24 hours in all groups, but the amount was significantly higher (P < .05) in group B at 1, 6, and 12 hours. The paclitaxel amount in navigated balloons from group A was significantly lower than in other groups (P < .05). ConclusionsPaclitaxel concentration in an atherosclerotic lesion model immediately after DEB angioplasty is nearly fourfold higher than in a healthy artery. Paclitaxel remains in the bloodstream longer when a universal state of fat arterial infiltration is achieved. These findings could have clinical implications, as studies testing commercial drug-eluting devices on healthy animals may be underestimating paclitaxel arterial uptake.