title: Dialyzability and pharmacokinetics of sitafloxacin following multiple oral dosing in infected hemodialysis patients.
abstract: The pharmacokinetics and dialyzability of oral sitafloxacin, a newly available quinolone, in infected intermittent hemodialysis patients have not been reported previously. Seven infected maintenance hemodialysis patients lacking residual renal function were enrolled. Sitafloxacin (50 mg after hemodialysis on the first day, on the next day and 4 h before scheduled hemodialysis session on the 3rd day) was orally administered. On the 3rd day, blood was taken from arterial and venous sides before and 2 and 4 h after session initiation. Another sampling was performed 1 h after the session and on the 5(th) day of the study. Pharmacokinetic parameters and dialyzability of sitafloxacin were evaluated. All patients exhibited improved symptoms without major problems. Drug concentrations in all arterial samples were above the MIC of targeted bacteria. Dialyzer clearance and elimination fraction were 49.9 ± 0.9 mL/min per m(2) and 53.3 ± 2.1%, respectively. Apparent half-life during dialysis session was significantly shorter than that after the session (4.0 ± 0.4 and 46.5 ± 3.6 h, during and after the session, respectively). Dialyzer clearance was positively correlated with urea reduction ratio and negatively correlated with serum albumin concentration. About 23% of the drug in the body was removed by dialysis. Rebound of the drug concentration after the dialysis was not seen. Oral dosing of this drug at 50 mg daily in maintenance hemodialysis patients provides a safe drug concentration compatible with that of healthy subjects orally receiving 100 mg daily. Because a significant amount of the drug was removed, administration might be undertaken after the dialysis session.
authors.affiliation: Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba Hemodialysis Unit, Moka Hospital, Moka, Japan. tsuruoka@nms.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Yokota
authors.forename: Tokie
authors.initials: T
authors.lastname: Hayasaka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Saito
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism; D014508:Urea / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012709:Serum Albumin; D014508:Urea; C076246:sitafloxacin