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首页> 外文期刊>Iranian red crescent medical journal >Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation
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Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation

机译：椎旁植入后利福喷汀聚乳酸缓释微球在兔体内的释药特性和组织分布

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Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. Objectives: The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation. Methods: This study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang Medical University. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomly divided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebral muscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biological internal standard was used to determine the drug concentrations in samples. Results: In group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points (P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P < 0.05); for days 21, 35, 46, and 60, the differences in rifapentine concentrations between two sequential time points were not statistically significant (P > 0.05). In group B, the differences in rifapentine concentration between days 3 and 10 in vertebral bone and in paravertebral muscles were statistically significant (P < 0.05). Rifapentine was detected in the vertebral bone tissue in the group C animals. The rifapentine concentrations between two sequential time points were statistically significant (P < 0.05). Rifapentine could not be detected in the paravertebral muscles 46 days after the operation. The differences in rifapentine concentrations between two sequential time points among days 3, 10, 21, and 35 were statistically significant (P < 0.05). Conclusions: After paravertebral implantation of rifapentine polylactic acid sustained-release microspheres, the concentration of rifapentine in local vertebral bone tissues was maintained above the TB minimum inhibitory concentration for up to 60 days with no apparent accumulation of the drug in other tissues.
机译：耐药性结核病（TB）和与人类免疫缺陷病毒（HIV）感染相关的结核病的发病率急剧上升，从而加剧了结核病控制方面的挑战。控制药物释放并增加局部药物浓度的新的结核病治疗药物配方，将对减轻毒性副作用和提高抗结核药物的临床疗效产生重大影响。目的：目的是观察利福喷汀聚乳酸缓释微球在体内的缓释特性以及椎旁植入后利福喷汀在其他组织中的蓄积情况。方法：本研究是一项基础动物实验研究，始于2014年7月17日在新疆医科大学第五附属医院。一百零八只新西兰白兔（体重为2.8-3.0千克，雄性和雌性，中国​​）被随机分为三组，每组36只。在手术后的不同时间点，从肝脏，肺，肾脏，椎骨和椎旁肌采集血液和组织样本。使用具有生物内标物的高效液相色谱（HPLC）分析来确定样品中的药物浓度。结果：在A组中，在任何两个时间点之间，肝脏中的利福喷汀浓度均未检测到显着差异（P> 0.05）。然而，第10天和第21天之间的利福喷汀浓度差异具有统计学意义（P <0.05）;在第21、35、46和60天，两个连续时间点之间的利福喷丁浓度差异无统计学意义（P> 0.05）。在B组中，椎骨和椎旁肌肉中第3天和第10天之间的利福喷丁浓度差异具有统计学意义（P <0.05）。在C组动物的椎骨组织中检测到利福喷汀。两个连续时间点之间的利福喷丁浓度具有统计学意义（P <0.05）。术后46天未在椎旁肌肉中检测到利福喷汀。在第3、10、21和35天的两个连续时间点之间，利福喷汀浓度的差异具有统计学意义（P <0.05）。结论：椎旁植入利福喷汀聚乳酸缓释微球后，局部椎骨组织中利福喷汀的浓度可维持在TB最低抑制浓度以上长达60天，而其他组织中没有明显的药物蓄积。

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