title: Hepatobiliary elimination of temafloxacin.
abstract: The biliary excretion of temafloxacin and temafloxacin glucuronide was characterised in this study after administration of a single oral temafloxacin 600mg dose to 8 patients with T-tube drainage of the common bile duct inserted after cholecystectomy or choledochotomy. High performance liquid chromatographic analyses of plasma, urine and bile samples collected during the 72h after temafloxacin administration showed that biliary concentrations of unchanged temafloxacin followed a time-course parallel to plasma concentrations but were 5- to 10-fold higher. Biliary temafloxacin peak concentrations ranged from 18.74 to 64.35 mg/L and time to peak concentrations from 0.71 to 10.23h. Mean hepatobiliary clearance of temafloxacin was 3.10 ml/min (0.19 L/h) when calculated for the unchanged drug and 1.43 ml/min (0.09 L/h) when calculated for its biliary excretion as glucuronic acid conjugates. Patients with higher bile production had markedly higher clearance of both temafloxacin and temafloxacin glucuronide. The elimination time-course of the conjugate in bile generally paralleled those of temafloxacin in bile and plasma, although there was a lag in the rate of appearance of the conjugate in bile. Biliary excretion of unchanged temafloxacin and temafloxacin glucuronide accounted for approximately 2.2 and 1% of the administered dose, respectively. Thus, it appears that hepatobiliary elimination of temafloxacin and its glucuronide acid accounts for only a small fraction of total temafloxacin clearance. Nonetheless, concentrations attained in the bile are far above the minimum inhibitory concentration values of pathogens relevant in biliary tract infections.
authors.affiliation: IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Sörgel
authors.forename: G R
authors.initials: GR
authors.lastname: Granneman
authors.forename: G
authors.initials: G
authors.lastname: Mahr
authors.forename: P
authors.initials: P
authors.lastname: Kujath
authors.forename: W
authors.initials: W
authors.lastname: Fabian
authors.forename: P
authors.initials: P
authors.lastname: Nickel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry*; D002763:Cholecystectomy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C054745:temafloxacin