Optimum Peripheral Drug Deposition in Patients with Cystic Fibrosis

Abstract

In order to identify the optimum particle size and breathing pattern for high peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional deposition in these patients was studied systematically as a function of particle size, inhalation volume and flow rate. Regional deposition was assessed using the single-breath regional deposition technique in which the concentration profile of inhaled and exhaled non-radioactive, monodisperse test particles is analyzed. Using this technique particle deposition within the functional dead space volume and peripherally can be assessed. Regional deposition was measured in 12 patients with cystic fibrosis using 2, 3, 4, and 5.5 microm particles, inhalation volumes of 500, 1000, 1500, and 2000 cm(3), and inhalation flow rates of 100, 250, 500, and 750 cm(3)/sec. Peripheral deposition was highest when 2-3-microm particles were inhaled with air-flow rates of 250-500 cm(3)/sec. With these parameters peripheral deposition increased with increasing inhalation volume and reached values of about 60% of the total drug inhaled. It has been shown that high peripheral drug deposition can be achieved in patients with CF when inhalations are performed using an optimized combination of particle size and breathing pattern.

α1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

“…Accordingly, each subject received an individually programmed SMART CARD (Inamed Gmbh, Gmü nden, Germany) to be used in conjunction with the AKITA1 device (Inamed GmbH), which determined the respective inhalation pattern with bronchial or peripheral deposition [19]. During the following 2-week run-in period, the subjects inhaled an isotonic saline solution once daily in order to get used to the inhalation pattern.…”

“…Patients were randomly assigned to either bronchial or peripheral deposition, according to the method described by BRAND et al [19].…”

Effect of Drug Targeting Nebulization on Lung Deposition: A Randomized Crossover Scintigraphic Comparison Between Central and Peripheral Delivery

“…A slow inspiratory flow was previously related to a better peripheral deposition after a single breath of an inert aerosol. 21 Even if the O/I ratio was Ͼ 1 independent of the mode, the highest O/I ratio was not related to one of the 2 modalities. It could be explained by the variability of airway geometry between subjects.…”

“…19 Moreover, they are able to target the peripheral parts of the lungs by modifying the delivery method. 20,21 The aim of this study was to quantify total and peripheral lung deposition by drug targeting nebulization and to compare the peripheral and central targeted modalities of administration.…”

The National Consensus Project* «cystic Fibrosis: Definition, Diagnostic Criteria, and Therapy». Section «inhalation Therapy» (Abridged)

“…Важную роль в процессе ингаляции играют частицы менее 5 мкм -респирабельная фракция аэрозоля, которая осаждается в мелких бронхах и бронхиолах. У большин-ства небулайзеров респирабельная фракция составляет не менее 60% от произведенного аэрозоля [37,38].…”