title: Pharmacokinetics of ertapenem in colorectal tissue.
abstract: BACKGROUND
  There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling.
  
  
  METHODS
  Patients ≥18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT.
  
  
  RESULTS
  Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14-15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≥90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT(>)(MIC) = 20%) and up to 0.25-0.5 mg/l for the near-maximal killing target (40% fT(>)(MIC)).
  
  
  CONCLUSIONS
  Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.
authors.affiliation: Department of Visceral Surgery, University of Ulm, Ulm, Germany. mathias.wittau@uniklinik-ulm.de
authors.forename: M
authors.initials: M
authors.lastname: Wittau
authors.forename: J
authors.initials: J
authors.lastname: Scheele
authors.forename: J B
authors.initials: JB
authors.lastname: Bulitta
authors.forename: B
authors.initials: B
authors.lastname: Mayer
authors.forename: V
authors.initials: V
authors.lastname: Kaever
authors.forename: H
authors.initials: H
authors.lastname: Burhenne
authors.forename: D
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: R
authors.initials: R
authors.lastname: Isenmann
authors.forename: C
authors.initials: C
authors.lastname: Brockschmidt
mesh_terms: D000328:Adult; D000368:Aged; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000077727:Ertapenem; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D011485:Protein Binding; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution; D047090:beta-Lactams / Q000493:pharmacokinetics*
chemical_list: D047090:beta-Lactams; D000077727:Ertapenem