Le Brun P P H, de Boer A H, Mannes G P M, de Fraîture D M I, Brimicombe R W, Touw D J, Vinks A A, Frijlink H W, Heijerman H G M
Central Hospital Pharmacy, PO Box 43100, 2504 AC The Hague, The Netherlands.
Eur J Pharm Biopharm. 2002 Jul;54(1):25-32. doi: 10.1016/s0939-6411(02)00044-9.
The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.
本研究的目的是在6名健康志愿者和5名囊性纤维化患者中，使用一种新的黏菌素干粉吸入系统进行原理验证研究。所有受试者均被要求吸入25毫克硫酸黏菌素干粉。患者还被要求雾化吸入160毫克甲磺酸盐黏菌素溶液。测定黏菌素血清浓度作为比较两种给药方式的间接参数。进行了肺功能测试。吸入25毫克干粉后，志愿者的血清黏菌素峰值浓度在14至59微克/升之间。在患者中，雾化吸入160毫克甲磺酸盐黏菌素溶液后的峰值浓度在18至64微克/升之间，吸入25毫克硫酸黏菌素干粉后的峰值浓度在77至159微克/升之间。志愿者吸入干粉后以及患者雾化吸入溶液后，肺功能测试无显著差异。在一些患者中，吸入干粉后观察到肺功能下降以及中度至重度咳嗽。这种新型黏菌素吸入器为雾化黏菌素提供了一种有吸引力的替代方法，并且受到患者的高度评价。患者肺功能下降和咳嗽是一个缺点，这可能通过降低剂量和进一步改进新剂型来克服。
