Influence ofRifampin onFleroxacin Pharmacokinetics

inplasma andurine weredetermined by reverse-phase high-performance liquid chromatography. Theextent ofhepatic enzyme induction byrifampin wasconfirmed byasignificant increase of6-13-hydroxycortisol urinary output from160.8 ± 41.4to544.8 ± 120.7 ,ug/4 h.Therewerenosignificant changes inthepeakfleroxacin concentration inplasma (6.3 ± 1.2 versus 6.2± 1.9mg/liter), timetomaximumconcentration offleroxacin inplasma (1.1 ± 0.9versus 1.3± 1.1 h),orrenal clearance (58.3 ± 16.4versus 61.9± 19.2mVmin). Theareaunderthecurve AUC(71.4 ± 15.8 versus 62.2± 13.7mg.h/liter) andtheterminal half-life offleroxacin (11.4 ± 2.2versus 9.2+ 1.1h)decreased (P< 0.05), while thetotal plasma clearance increased from97.7± 21.6to112.3 ± 25.8ml/min (P< 0.01). Despite beingstatistically significant, this15%increase intotal plasma clearance doesnotappear tobe clinically relevant. Metabolic clearance byNdemethylation wasincreased (6.9 ± 2.4versus 12.5 ± 3.2ml/min; P < 0.01), whereas clearance byNoxidation didnotchange (5.8 ± 1.1versus 5.8± 1.5ml/min). Fleroxacin elimination wasslightly increased (about 15%)through induction ofmetabolic clearance toN-demethylfleroxacin. Since fleroxacin levels remained abovetheMICfor90%oofthetested isolates ofmethicillinsusceptible S.aureus foratleast 24h,doseadjustment doesnotappear necessary, atleast forshort-term treatments.