Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity
Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity
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DOI：
10.1211/jpp.57.10.0007
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Vulto, AG
中科院分区：
文献类型：
--
作者：
Ruijgrok, EJ;Fens, MHA;Vulto, AG
本文研究了阿替霉素B脱氧胆酸盐（AMS-DOC）、阿替霉素B脂质体（L-AMB）、阿替霉素B脂质复合物（ABLC）和阿替霉素B胶体分散体（ABCD）的雾化吸入。测量产生的气溶胶液滴的颗粒尺寸。在健康大鼠中测量雾化后即刻和雾化后6周时肺中的阿替霉素B沉积和血液中的阿替霉素B浓度。在患有侵袭性肺曲霉病的持续性粒细胞减少大鼠中评价雾化阿替霉素B制剂的疗效。在真菌接种之后或之前给予治疗。终点是动物的存活率。AMB-DOC、L-AMB、ABLC和ABCD的气溶胶颗粒尺寸（以质量中值直径表示）分别为1.38、2.43、0.90和2.29 μ m。雾化后肺中的两性霉素B浓度直接超过烟曲霉菌的最低抑菌浓度，雾化后6周，在大鼠肺中仍检测到两性霉素B。真菌接种后16小时开始给药，与假给药大鼠相比，所有四种制剂的存活时间均显著延长。真菌接种前一周的预防性治疗导致所有四种制剂的存活期显著延长。在接种前两周给予气雾剂治疗仅对AMB-DOC和L-AMB有效，而在六周给予气雾剂治疗仅导致L-AMB的存活期显著延长。所有市售的两性霉素B制剂都可以有效雾化，并且可能对侵袭性肺曲菌病的预防性治疗有价值。
The nebulization of amphotericin B desoxycholate (AMS-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 mu m for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.