Abadal J M, Vazquez Esther, Morales Miguel, Toro Arturo, Quintana Manuel, Araujo Miguel
Vascular and Interventional Radiology Department, Hospital Universitario Severo Ochoa, 28911, Leganes, Madrid, Spain.
Vascular Surgery Department, Hospital Universitario Severo Ochoa, Madrid, Spain.
Cardiovasc Intervent Radiol. 2016 Aug;39(8):1152-8. doi: 10.1007/s00270-016-1346-x. Epub 2016 Apr 19.
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.
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.
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.
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.
本研究旨在评估在猪髂动脉损伤模型中，使用不同药物载量的两种紫杉醇（PTX）药物涂层球囊（DCB）的药代动力学和组织吸收情况。
28头猪被随机分为两组。在B1组中，使用含1.0 μg/mm² PTX的DCB进行血管成形术；在B3组中，使用含3.0 μg/mm² PTX的DCB进行血管成形术。在荧光透视下，采用髂动脉过度扩张模型进行血管成形术。在1、5、30分钟、1、7和28天，用液相色谱质谱法测量血液和血管壁中的PTX。分析球囊中剩余的药物。
B3组血液中PTX的平均含量显著高于B1组，分别为0.269±0.085 μg/ml和0.218±0.085 μg/ml；p = 0.01。血管成形术后1分钟检测到血液中PTX浓度峰值，术后24小时未检测到PTX。B1组（15.24±21.29 ng/mg）和B3组（15.68±16.33 ng/mg）治疗后的髂动脉平均动脉壁浓度，以及在不同时间点测量的PTX壁浓度，均无统计学显著差异。B1组检测球囊中剩余药物的平均值较低，占初始剂量的8%。
使用3.0 μg/mm² DCB时血液中的PTX较高，药物浓度峰值出现在1分钟，尽管术后24小时未检测到药物，且与载药量无关。本研究表明，与常用剂量的DCB（3.0 μg/mm²）相比，低剂量DCB（1.0 μg/mm²）在动脉壁摄取方面无差异，这表明DCB中的药物剂量可以降低，以获得相似的临床效果。
