Pharmacokinetic Evaluation of Two Paclitaxel-Coated Balloons with Different Drug Load in a Short-Term Porcine Study.
OBJECTIVE
The aim of the study was to evaluate the pharmacokinetics and tissue absorption of 2 paclitaxel (PTX) drug-coated balloons (DCB) using different drug loads in a porcine-injured iliac artery model.


METHODS
Twenty-eight pigs were randomized into 2 groups. In group B1, angioplasty was performed with a 1.0 µg/mm(2) DCB with PTX and in group B3, with a 3.0 µg/mm(2) DCB with PTX. An overstretched model of the iliac artery was used for angioplasty under fluoroscopy. Blood and vessel wall PTX were measured with liquid-chromatography mass spectrometry at 1, 5, 30 min, 1, 7, and 28 days. Remaining drug in the balloon was analyzed.


RESULTS
Mean PTX in blood was significantly higher in the group B3 0.269 ± 0.085 µg/ml compared with the B1 0.218 ± 0.085 µg/ml; p = 0.01. Peak blood PTX concentration was detected at 1 min, and PTX was undetectable 24 h post-angioplasty. There were no statistically significant differences in the mean arterial wall concentration from the treated iliac artery between group-B1 (15.24 ± 21.29 ng/mg) and B3 (15.68 ± 16.33 ng/mg), or in the PTX wall concentration measured at different time points. Mean remaining drug in assayed balloons was lower for group-B1 and represented 8 % of the initial dose.


CONCLUSIONS
Blood PTX was higher when using 3.0 µg/mm(2) DCB, with a peak drug concentration at 1-min, although the drug was undetectable at 24 h, independently of the loading dose. This study demonstrates no difference in arterial wall uptake of a low dose DCB (1.0 µg/mm(2)), when compared to a common dose DCB (3.0 µg/mm(2)) suggesting that the dose of drug in the DCB could be reduced obtaining a similar clinical effect.
Vascular and Interventional Radiology Department, Hospital Universitario Severo Ochoa, 28911, Leganes, Madrid, Spain. jmabadal@yahoo.es.
J M
JM
Abadal
Vascular Surgery Department, Hospital Universitario Severo Ochoa, Madrid, Spain.
Esther
E
Vazquez
Vascular and Interventional Radiology Department, Hospital Universitario Severo Ochoa, 28911, Leganes, Madrid, Spain.
Miguel
M
Morales
Vascular and Interventional Radiology Department, Hospital Universitario Severo Ochoa, 28911, Leganes, Madrid, Spain.
Arturo
A
Toro
Vascular Surgery Department, Hospital Universitario Severo Ochoa, Madrid, Spain.
Manuel
M
Quintana
Vascular Surgery Department, Hospital Universitario Severo Ochoa, Madrid, Spain.
Miguel
M
Araujo
D000800:Angioplasty, Balloon / Q000295:instrumentation* / Q000379:methods*; D000818:Animals; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia / Q000628:therapy; D007083:Iliac Artery / Q000473:pathology*; D008297:Male; D017239:Paclitaxel / Q000493:pharmacokinetics*; D034421:Sus scrofa; D013552:Swine; D050257:Tubulin Modulators / Q000493:pharmacokinetics
D020099:Coated Materials, Biocompatible; D050257:Tubulin Modulators; D017239:Paclitaxel
Angioplasty; Drug-coated balloons; Neointimal hyperplasia; Paclitaxel