Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.
Claire M Naftalin, Rupangi Verma, Meera Gurumurthy, Kim Hor Hee, Qingshu Lu, Benjamin Chaik Meng Yeo, Kin Hup Tan, Wenwei Lin, Buduo Yu, Kok Yong Seng, Lawrence Soon-U Lee, Nicholas I Paton
Author Information
Claire M Naftalin: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. claire_naftalin@nuhs.edu.sg.
Rupangi Verma: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Meera Gurumurthy: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Kim Hor Hee: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Qingshu Lu: Singapore Clinical Research Institute, Singapore, Singapore.
Benjamin Chaik Meng Yeo: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Kin Hup Tan: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Wenwei Lin: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Buduo Yu: Investigational Medicine Unit, National University Health System, Singapore, Singapore.
Kok Yong Seng: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Lawrence Soon-U Lee: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Nicholas I Paton: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA -0.10 ± 0.13ΔlogCFU versus -0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference -0.01, 95% CI -0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.
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