Pharmacokinetics of rifampicin after repeated intra-tracheal administration of amorphous and crystalline powder formulations to Sprague Dawley rats

A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation

“…Delivering rifampicin by inhalation is a potential alternative to achieve high drug concentration in the lungs as well as systemic circulation with a smaller dose. After pulmonary delivery, high blood concentration can be achieved at a smaller dose than the oral dose due to rapid drug absorption through the large surface area and minimal drug metabolism in the lung [ 47 , 48 ], which may reduce the likelihood of dose-dependent systemic toxicity of rifampicin. Inhaled rifampicin has a huge potential for clinical translation and could be used as an adjunct to current oral anti-TB regimens for improved therapeutic outcomes in TB patients.…”

“…It was observed that repeated intra-tracheal administration of high-dose rifampicin (up to 50 mg/kg) powder formulations were safe to rat lungs and liver, and intra-tracheal rifampicin decreased the drug burden on the liver compared to oral rifampicin, as suggested by no rise in the serum alanine transaminase (ALT) activity in repeated dose 25 mg/kg and single dose 50 mg/kg intratracheal administration groups compared to the nontreated control group [ 74 ]. Similarly, rifampicin powder formulations delivered via the inhaled route resulted in significantly higher systemic bioavailabilities of rifampicin (193.1 ± 37.9 and 126.3 ± 20.3 μg·h/mL) compared to that from oral rifampicin (87.4 ± 64.7 and 71.5 ± 11.0 μg·h/mL) at the same dose after a single administration of 50 mg/kg rifampicin for each formulation, respectively [ 47 ].…”