title: Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin.
abstract: OBJECTIVE
  Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals.
  
  
  METHODS
  A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method.
  
  
  RESULTS
  Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C max to MIC and AUC 0-12 to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX.
  
  
  CONCLUSIONS
  Concomitant RMP administration caused a significant decrease in C max and AUC 0-12 of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes.
authors: National Institute for Research in Tuberculosis (ICMR), Chennai, India. geetha202@rediffmail.com
authors: Geetha
authors: G
authors: Ramachandran
authors: A K
authors: AK
authors: Hemanth Kumar
authors: R
authors: R
authors: Srinivasan
authors: A
authors: A
authors: Geetharani
authors: P
authors: P
authors: Sugirda
authors: B
authors: B
authors: Nandhakumar
authors: R
authors: R
authors: Nandini
authors: C B
authors: CB
authors: Tharani
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001372:Aza Compounds / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D024841:Fluoroquinolones; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin
references: Int J Tuberc Lung Dis. 2006 Jun;10(6):605-12
references: 16776446
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Apr 15;877(11-12):1205-8
references: 19286427
references: Clin Pharmacokinet. 2001;40 Suppl 1:1-9
references: 11352436
references: Antimicrob Agents Chemother. 2007 Aug;51(8):2861-6
references: 17517835
references: Am J Respir Crit Care Med. 2003 Dec 1;168(11):1342-5
references: 12917230
references: Arch Intern Med. 2002 May 13;162(9):985-92
references: 11996607
references: Drugs. 2001;61(1):9-18
references: 11217874
references: J Antimicrob Chemother. 1999 May;43 Suppl B:83-90
references: 10382880
references: Int J Tuberc Lung Dis. 1998 Apr;2(4):265-71
references: 9559396
references: Clin Infect Dis. 2007 Oct 15;45(8):1001-7
references: 17879915
references: Br J Clin Pharmacol. 1999 Aug;48(2):168-79
references: 10417493
references: Antimicrob Agents Chemother. 2007 Feb;51(2):576-82
references: 17145798
references: Am J Respir Crit Care Med. 2004 Nov 15;170(10):1131-4
references: 15306535
references: Antimicrob Agents Chemother. 2003 Feb;47(2):653-7
references: 12543673
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jan 5;766(1):181-7
references: 11820293
references: Clin Pharmacokinet. 2003;42(9):819-50
references: 12882588
references: Antimicrob Agents Chemother. 2004 Nov;48(11):4473-5
references: 15504887
references: Am J Respir Crit Care Med. 2004 Feb 1;169(3):421-6
references: 14578218