title: Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy.
abstract: BACKGROUND
  The duration of time for which the serum levels exceed the minimum inhibitory concentration (MIC) is an important pharmacokinetics (PK)/pharmacodynamics (PD) parameter correlating with efficacy for the antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD in patients undergoing continuous renal replacement therapy (CRRT). The purpose of this study was to examine the PK and safety of CTRX in patients undergoing CRRT in order to establish safer and more effective regimens.
  
  
  METHODS
  CTRX (1 g once a day) was intravenously administered four or more times to nine patients undergoing CRRT. Blood was collected after administration to measure CTRX concentrations in serum and the filtration fraction of CRRT by high-performance liquid chromatography. In addition to calculating PK parameters from serum CTRX, we (a) estimated by simulation CTRX concentrations when the dose interval was extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from CTRX concentrations in the filtration fraction, and (c) assessed the safety of CTRX use.
  
  
  RESULTS
  Total body clearance and the half-life of CTRX were 7.46 mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was found in the filtration fraction, and the estimated clearance by CRRT was about 70% of total body clearance. Simulations revealed that even when the dose interval is increased to 2 or 3 days, CTRX would retain its efficacy.
  
  
  CONCLUSIONS
  Our findings suggest that, depending on the condition of patients undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC ≤2 µg/mL, even when extending the dose interval.
authors: Koji
authors: K
authors: Goto
authors: Yuhki
authors: Y
authors: Sato
authors: Norihisa
authors: N
authors: Yasuda
authors: Seigo
authors: S
authors: Hidaka
authors: Yosuke
authors: Y
authors: Suzuki
authors: Ryota
authors: R
authors: Tanaka
authors: Tetsuya
authors: T
authors: Kaneko
authors: Ko
authors: K
authors: Nonoshita
authors: Hiroki
authors: H
authors: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002443:Ceftriaxone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D017582:Renal Replacement Therapy / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone