Diot P, Dequin P F, Rivoire B, Gagnadoux F, Faurisson F, Diot E, Boissinot E, Lemarié E
Service de pneumologie et d'explorations fonctionnelles respiratoires, UPRES-EA 2638, Tours.
Rev Mal Respir. 1999 Jun;16(3):277-85.
Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides) and amphotericin B can be administered by aerosol. This route of administration is not officially approved and it constitutes an empirical approach which has benefited from recent research which is summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics have also to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Distinction between good and bad nebulizers does not depend upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent a significant progress. Finally, adminnistration of anti infectious aerosols requires a new pharmacological approach to monitor treatment and urinary assays are promising.
抗感染药物如喷他脒、抗生素(主要是黏菌素和氨基糖苷类)及两性霉素B可通过雾化给药。这种给药途径未获官方批准,属于一种经验性方法,它受益于近期的研究,现总结如下。最根本的问题与雾化过程,尤其是超声雾化,对药物抗感染特性的潜在有害影响有关。黏菌素因其多肽结构先天不稳定而被选作参照,结果证明它对高频超声具有抗性,这对氨基糖苷类或β-内酰胺类等其他分子来说是令人鼓舞的。雾化器的特性也必须予以考虑。使用超声雾化器和喷射雾化器都能从两性霉素B混悬液和黏菌素中产生气溶胶。区分优质和劣质雾化器并不取决于雾化药物所涉及的物理过程,而是取决于设备的内在特性及其对已知药物的性能表现。可吸入范围内气溶胶的吸入量必须很高,剂量测定雾化器代表了一项重大进展。最后,抗感染气溶胶的给药需要一种新的药理学方法来监测治疗,尿液检测很有前景。