title: Pharmacokinetics of ceftriaxone in plasma and bone of patients undergoing hip or knee surgery.
abstract: OBJECTIVE
  Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before surgery. It is controversial in which antibiotic is the treatment of choice for this purpose. One possibility is the cephalosporin ceftriaxone. Here, we wanted to know if effective tissue concentrations are reached.
  
  
  METHODS
  We studied plasma and bone kinetics of ceftriaxone in orthopaedic patients (n = 22) treated with ceftriaxone (2 g) immediately prior operation. Plasma samples were withdrawn before and at three time points after ceftriaxone infusion. After bone replacement, extracts from cancellous bone or cortical bone were obtained, and ceftriaxone was quantified using column chromatography.
  
  
  RESULTS
  The plasma kinetics of ceftriaxone and distribution into bone were analysed using a population approach (ADAPT 5). The population mean of the area under the curve (AUC) was 140 mg h/l. A cancellous bone to plasma concentration ratio of 1.12 ± 1.29 was achieved 5 h after start of infusion. The half-life of uptake into the cortical bone was less (8.4 h) than into cancellous bone (12.1 h, P < 0.05).
  
  
  CONCLUSIONS
  Under these experimental conditions, concentrations of ceftriaxone in cancellous and cortical bone should be adequate to protect the patients against usual ceftriaxone-sensitive nosocomial infections and are substantially lower than the plasma concentrations.
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Faculty, University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gergs
authors.forename: Tobias
authors.initials: T
authors.lastname: Clauss
authors.forename: Dorothea
authors.initials: D
authors.lastname: Ihlefeld
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.forename: Klaus
authors.initials: K
authors.lastname: Pönicke
authors.forename: Gunther O
authors.initials: GO
authors.lastname: Hofmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D001842:Bone and Bones / Q000378:metabolism*; D002443:Ceftriaxone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D003428:Cross Infection / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone
keywords: HPLC; antibiotics; bone surgery; ceftriaxone; population pharmacokinetics