A Spray-Dried Combination of Capreomycin and CPZEN-45 for Inhaled Tuberculosis Therapy
A Spray-Dried Combination of Capreomycin and CPZEN-45 for Inhaled Tuberculosis Therapy
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DOI：
10.1016/j.xphs.2019.05.024
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发表时间：
2019-10-01
影响因子：
3.8
通讯作者：
Carter, Darrick
中科院分区：
文献类型：
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作者：
Pitner, Ragan A.;Durham, Phillip G.;Carter, Darrick
结核病(TB)仍然是可归因于单一病原体的最严重的传染病。各种药物已经作为干粉进行了肺部给药评估：硫酸卷曲霉素已经显示出疗效，可以通过高剂量吸入安全地传递给人类志愿者，而CPZEN-45是一种新药，也被证明可以杀死耐药结核病。这里的研究通过喷雾干燥将这些作用机制不同的药物组合成单一颗粒的成分，产生了一种新的组合药物疗法。喷雾干燥复合粉剂是在适合肺部给药的气动粒度范围内制备的。理化保存期为6个月。卷曲霉素和CPZEN-45喷雾干燥后的复合粉剂对粘蛋白的亲和力中等，表明释放的药物在肺内不会与这些粘蛋白结合，具有杀菌作用。在豚鼠体内的药代动力学研究表明，直接肺部给药和随后的全身生物利用度后，药物的局部浓度较高。还需要进一步的研究来证明这种组合的体内疗效，以确认这种新组合的治疗潜力。(C)2019年美国药剂师协会(R)。爱思唯尔公司出版，版权所有。
Tuberculosis (TB) remains the single most serious infectious disease attributable to a single-causative organism. A variety of drugs have been evaluated for pulmonary delivery as dry powders: capreomycin sulfate has shown efficacy and was safely delivered by inhalation at high doses to human volunteers, whereas CPZEN-45 is a new drug that has also been shown to kill resistant TB. The studies here combine these drugs-acting by different mechanisms-as components of single particles by spray-drying, yielding a new combination drug therapy. The spray-dried combination powder was prepared in an aerodynamic particle size range suitable for pulmonary delivery. Physicochemical storage stability was demonstrated for a period of 6 months. The spray-dried combination powders of capreomycin and CPZEN-45 have only moderate affinity for mucin, indicating that delivered drug will not be bound by these mucins in the lung and available for microbicidal effects. The pharmacokinetics of disposition in guinea pigs demonstrated high local concentrations of drug following direct administration to the lungs and subsequent systemic bioavailability. Further studies are required to demonstrate the in vivo efficacy of the combination to confirm the therapeutic potential of this novel combination. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.