PDF(Pubmed)
Abstract：
Pulmonary Mycobacterium avium-intracellulare complex (MAC) disease is a typical non-tuberculous mycobacterial infection. The incidence of pulmonary MAC is increasing worldwide. This study aimed to clarify the pharmacokinetic parameters of anti-pulmonary MAC disease drugs in silkworms. The pharmacokinetic parameters investigated included maximum concentration, area under the concentration-time curve, total clearance, and volume of distribution at steady-state. In addition, protein-binding rates, fat body transferability, and drug-drug interactions were examined. Antibiotic concentrations were measured using a validated high-performance liquid chromatography-mass spectrometry method. Among the antibiotics investigated, amikacin was not eliminated from silkworms during the 48-h observation period. In contrast, dose-proportional pharmacokinetics were observed in silkworms for all antibiotics tested, except for amikacin. Protein-binding rates in hemolymph for clarithromycin, azithromycin, rifampicin, ethambutol, and amikacin were 39.6 ± 3.0%, 39.5 ± 4.3%, 76.3 ± 3.2%, 20.9 ± 4.2%, and 73.1 ± 4.7%, respectively (mean ± standard deviation). The distribution of antibiotics in the fat bodies of silkworms was related to drug lipophilicity. No drug-drug interactions were observed in the silkworms. The pharmacokinetics of these drugs in silkworms differed significantly from those in humans. Therefore, while it is challenging to predict the pharmacokinetics of these drugs in humans based on silkworm data, the silkworm infection model has facilitated a comprehensive assessment of the relationship between antibiotic exposure and efficacy.
摘要：
肺分枝杆菌-细胞内复合体(MAC)病是一种典型的非结核分枝杆菌感染。在世界范围内,肺MAC的发病率正在增加。本研究旨在阐明抗肺MAC病药在家蚕体内的药代动力学参数。研究的药代动力学参数包括最大浓度，浓度-时间曲线下的面积，总间隙,和稳定状态下的分布量。此外,蛋白质结合率，脂肪的身体可转移性，和药物相互作用进行了检查。使用经过验证的高效液相色谱-质谱方法测量抗生素浓度。在调查的抗生素中，在48小时的观察期内，未从蚕中消除阿米卡星。相比之下,在家蚕中观察到所有测试的抗生素的剂量比例药代动力学，除了阿米卡星.克拉霉素在血淋巴中的蛋白结合率，阿奇霉素,利福平,乙胺丁醇,阿米卡星为39.6±3.0%，39.5±4.3%,76.3±3.2%,20.9±4.2%,73.1±4.7%，分别为(平均值±标准偏差)。抗生素在家蚕脂肪体中的分布与药物亲脂性有关。在家蚕中未观察到药物-药物相互作用。这些药物在家蚕中的药代动力学与在人类中的显着不同。因此,尽管根据家蚕数据预测这些药物在人体中的药代动力学具有挑战性，家蚕感染模型有助于全面评估抗生素暴露与疗效之间的关系。
