Jornal de doenças infecciosas e terapia

Abstrato

Inhaled, Nebulized Clofazimine for the Treatment of Pulmonary Nontuberculous Mycobacteria Disease Offers the Prospect of Convenient Dosing and Prolonged Activity

Thomas Hofmann, Michael Castagna

Orally or intravenously administered antibiotics have been successfully reformulated for delivery via inhalation and treatment of serious, chronic lung infections. Oral clofazimine has shown microbiological efficacy in patients with pulmonary nontuberculous mycobacterial (NTM) disease, a condition that is increasingly prevalent and associated with substantial morbidity. However, systemic administration of clofazimine can lead to drug accumulation in extrapulmonary tissues and clinically significant adverse reactions in non-target organs such as gastrointestinal side effects, QT prolongation, and skin discoloration. To overcome these limitations, an inhaled formulation of clofazimine has been  developed and tested preclinically and in healthy human volunteers. Preliminary evidence suggests that inhalation of clofazimine can achieve drug concentrations in lung tissue greater than the minimal inhibitory concentration (MIC) for prolonged periods and relatively low drug concentrations in plasma, potentially broadening the therapeutic index. In this article, we review the available data for inhaled clofazimine and highlight its potential as a treatment for pulmonary NTM disease