title: Pharmacokinetics and pharmacodynamic target attainment of intravenous pazufloxacin in the bile of patients undergoing biliary pancreatic surgery.
abstract: The study aimed to characterize the pharmacokinetics and pharmacodynamics of pazufloxacin (PZFX) in bile and to identify optimal dosing regimens. Pazufloxacin 500 mg was administered via a 0·5-hour intravenous infusion to 10 patients with endoscopic nasal bile drainage before or after biliary pancreatic surgery. Both blood and bile samples were collected pre-dose and at the end of infusion (0·5 hours) and for up to 5 hours thereafter. Concentrations of PZFX were determined using high-performance liquid chromatography. Noncompartmental and compartmental pharmacokinetic parameters were estimated, and Monte Carlo simulation was conducted to evaluate the pharmacodynamic exposure of PZFX in bile. The bile/plasma ratios were 3·58±1·15 in the area under the drug concentration-time curve (AUC) and 2·13±0·74 in the maximum drug concentration (Cmax). The delay in the time to Cmax, from plasma to bile, was 0·75±0·18 hours The probability of attaining pharmacodynamic targets (both AUC/MIC = 100 and Cmax/MIC = 8) in bile against a minimum inhibitory concentration (MIC) of 2 mg/l was >90% when PZFX was administered by a 0·5-hour infusion with 500 mg every 8 hours or 1000 mg every 12 hours These regimens provided an adequate antibacterial effect against the most common pathogens of biliary tract infections, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae with their MICs<2 mg/l.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Uegami
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Akira
authors.initials: A
authors.lastname: Nakashima
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shigemoto
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000368:Aged; D001646:Bile / Q000187:drug effects*; D001662:Biliary Tract Surgical Procedures; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010179:Pancreas / Q000187:drug effects / Q000601:surgery*; D013329:Structure-Activity Relationship
chemical_list: D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin
keywords: Pazufloxacin,; biliary tract infections; pharmacodynamics,; pharmacokinetics,; quinolones,