Evaluation of Proinflammatory Cytokines and Adverse Events in Healthy Volunteers upon Inhalation of Antituberculosis Drugs.
Inhalation therapy is a promising drug delivery approach for tuberculosis treatment. However, there is always concern about the safety of the dosage form by inhalation as it may induce inflammation. Developing a new dosage form for inhalation must include tests for its safety especially for the tumor necrosis factor (TNF)-α and interleukine (IL)-1β. The safety of four anti-tuberculosis (anti-TB) drugs administered via inhalation was assessed in healthy volunteers. Four anti-TB drugs; isoniazid, rifampicin, pyrazinamide and levofloxacin were prepared as dry powder and evaluated for uniformity of delivered dose and in vitro drug deposition. These four anti-TB dry powder formulations for inhalation met the criteria of uniformity of delivered dose and exhibited suitable size for lung delivery. Forty healthy volunteers were recruited and each was sequentially challenged with isoniazid, rifampicin, pyrazinamide and levofloxacin in different orders. Safety was monitored by measuring the pro-inflammatory cytokines in their sputum, lung function test, blood chemistry and adverse events. This study proves that all four anti-TB dry powders did not provoke inflammatory cytokines and are safe to healthy volunteers.
Nanotec-PSU Center of Excellence on Drug Delivery System and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University.
Teerapol
T
Srichana
Chaveewan
C
Ratanajamit
Siwasak
S
Juthong
Tan
T
Suwandecha
Nisa
N
Laohapojanart
Petchawan
P
Pungrassami
Alwar Ramanujam
AR
Padmavathi
D000280:Administration, Inhalation; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D007538:Isoniazid / Q000008:administration & dosage; D064704:Levofloxacin / Q000008:administration & dosage; D008081:Liposomes; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D013183:Sputum / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
D000995:Antitubercular Agents; D053583:Interleukin-1beta; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D011718:Pyrazinamide; D064704:Levofloxacin; D007538:Isoniazid; D012293:Rifampin