title: Evaluation of moxifloxacin for the treatment of tuberculosis: 3 years of experience.
abstract: Moxifloxacin (MFX) is a powerful second-line anti-tuberculosis (TB) agent, but the optimal dose has not yet been established and long-term safety data are scarce. We retrospectively reviewed the medical charts of TB patients treated at the Tuberculosis Centre Beatrixoord, University Medical Centre Groningen (Haren, the Netherlands) receiving MFX 400 mg once daily as part of their TB treatment between January 1 2006 and January 1 2009. Safety data and drug-drug interactions were evaluated. Efficacy was predicted based on the area under the concentration-time curve up to 24 h post-dosage (AUC(0-24h))/minimal inhibitory concentration (MIC) ratio. 89 patients were treated with a median dose of 6.9 mg · kg(-1) MFX once daily for a median period of 74 days. Discontinuation of therapy occurred in only three patients due to gastrointestinal side-effects and hypersensitivity. Pharmacokinetic analysis showed an AUC(0-24h)/MIC ratio <100 in eight out of 16 patients. A large variation in protein binding affected the unbound AUC(0-24h) considerably. These data show that MFX treatment was well tolerated in 89 patients receiving a dose of 400 mg once daily for a prolonged period. Considering the variability in (un)bound AUC(0-24h)/MIC ratio, therapeutic drug monitoring is recommended in selected patients (i.e. rifampicin co-medication; MIC ≥ 0.25 mg · L(-1)) to assess optimal therapy.
authors.affiliation: Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, PO box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: A D
authors.initials: AD
authors.lastname: Pranger
authors.forename: R
authors.initials: R
authors.lastname: van Altena
authors.forename: R E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
authors.forename: D R A
authors.initials: DR
authors.lastname: Uges
authors.forename: J G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: T S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: J W C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001372:Aza Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D009426:Netherlands; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin