title: Effect of coadministration of moxifloxacin and rifampin on Mycobacterium tuberculosis in a murine aerosol infection model.
abstract: Coadministration of moxifloxacin and rifampin was evaluated in a murine model of Mycobacterium tuberculosis pulmonary infection to determine whether the finding of antagonism documented in a hollow-fiber infection model could be recapitulated in vivo. Colony counts were followed in a no-treatment control group, groups administered moxifloxacin or rifampin monotherapy, and a group administered a combination of the two agents. Following 18 days of once-daily oral administration to mice infected with M. tuberculosis, there was a reduction in the plasma exposure to rifampin that decreased further when rifampin was coadministered with moxifloxacin. Pharmacodynamic analysis demonstrated a mild antagonistic interaction between moxifloxacin and rifampin with respect to cell kill in the mouse model for tuberculosis (TB). No emergence of resistance was noted over 28 days of therapy, even with monotherapy. This was true even though one of the agents in the combination (moxifloxacin) induces error-prone replication. The previously noted antagonism with respect to cell kill shown in the hollow-fiber infection model was recapitulated in the murine TB lung model, although to a lesser extent.
authors.affiliation: AstraZeneca India Pvt Ltd, Hebbal, Bangalore, India. Bala.Subramanian@AstraZeneca.com
authors.forename: V
authors.initials: V
authors.lastname: Balasubramanian
authors.forename: S
authors.initials: S
authors.lastname: Solapure
authors.forename: S
authors.initials: S
authors.lastname: Gaonkar
authors.forename: K N
authors.initials: KN
authors.lastname: Mahesh Kumar
authors.forename: R K
authors.initials: RK
authors.lastname: Shandil
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Deshpande
authors.forename: Naveen
authors.initials: N
authors.lastname: Kumar
authors.forename: K G
authors.initials: KG
authors.lastname: Vishwas
authors.forename: Vijender
authors.initials: V
authors.lastname: Panduga
authors.forename: Jitendar
authors.initials: J
authors.lastname: Reddy
authors.forename: Samit
authors.initials: S
authors.lastname: Ganguly
authors.forename: A
authors.initials: A
authors.lastname: Louie
authors.forename: G L
authors.initials: GL
authors.lastname: Drusano
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024841:Fluoroquinolones; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity*; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin; D012293:Rifampin