title: Penetration of moxifloxacin into liver tissue.
abstract: Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Justinger
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Martin G
authors.initials: MG
authors.lastname: Kees
authors.forename: Anne
authors.initials: A
authors.lastname: Kauffels
authors.forename: Katrin
authors.initials: K
authors.lastname: Hirschmann
authors.forename: Berit
authors.initials: B
authors.lastname: Kopp
authors.forename: Frieder
authors.initials: F
authors.lastname: Kees
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D001372:Aza Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000601:surgery; D008113:Liver Neoplasms / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin