Pharmacokinetics of Inhaled Rifampicin Porous Particles for Tuberculosis Treatment: Insight into Rifampicin Absorption from the Lungs of Guinea Pigs

Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration. RIF microparticles were prepared by spray drying a solution of RIF and l-leucine (9:1), and the resulting particles were characterized for their physicochemical properties. Animals received RIF either as intravenous solution (iv), as oral suspension of micronized RIF (ORS) and RIF-PPs (ORPP), or by insufflation of the PPs (IRPP). Plasma samples were collected at preselected time points, and bronchoalveolar lavage (BAL) was performed at the end of the study. RIF concentrations in biological samples were...