In vitro efficiency of Amikacin Inhale, a novel drug-device delivery system

Amikacin Inhale (NKTR-061, BAY41-6551) is a drug-device combination in clinical development for adjunctive treatment of intubated and mechanically ventilated patients with Gram-negative pneumonia. The product uses a proprietary vibrating mesh nebulizer system (PDDS Clinical) with amikacin sulfate formulated for inhalation (3.2 ml of 125 mg/ml amikacin solution) for a 10-day twice-daily course of therapy. It is designed for use with two delivery systems: one system for intubated patients (On-vent; Figure ​Figure1),1), and a second Handheld (HH) system for patients who are extubated before completing the course of therapy (Figure ​(Figure2).2). We investigated in vitro the amikacin lung dose delivered by PDDS Clinical. Figure 1 On-vent system with brown blinder shell for clinical trials. Figure 2 Handheld system with brown blinder shell for clinical trials. Methods An estimated lung dose (ELD) for On-vent setting was measured in vitro after collecting aerosolized amikacin from a filter at the end of an endotracheal tube during ventilation. The ELD for the HH device was calculated from the fine particle fraction (FPF <5 µm) post-mouthpiece, multiplied by the in vitro delivered dose post-mouthpiece. FPF <5 µm reflects lung deposition observed during phase 2 clinical trials [1]. Eighty-one nebulizers with volume median diameter (VMD) of 4.4 ± 0.5 µm and output rates of 0.23 ± 0.10 ml/minute were tested for each system. Delivered dose data were fit to the independent variables (that is, VMD and output rates) using a least-squares fit with 95% confidence limits.