title: An in vivo-in vitro study of cefepime and cefazolin dialytic clearance during high-flux hemodialysis.
abstract: OBJECTIVE
  To assess the influence of in vitro and in vivo hemodialysis with a new high-flux dialyzer on the clearance of cefazolin and cefepime; to assess the correlation of in vivo dialytic clearance of these antibiotics with blood flow rate; and to assess the correlation between in vitro and in vivo dialytic clearances of these antibiotics.
  
  
  METHODS
  Prospective, open-label, dialysis clearance study.
  
  
  METHODS
  A tertiary-care, university health science center.
  
  
  METHODS
  Five adults who received high-flux hemodialysis 3 times/week. Intervention. For the in vivo experiment, patients received a single intravenous infusion of cefazolin 1 g and cefepime 1 g before dialysis and then underwent a modified hemodialysis session. For the in vitro experiment, a buffered simulated plasma water (SPW) solution containing cefazolin and cefepime was used. Hemodialysis for both experiments was performed with use of a new high-flux polysulfone dialyzer.
  
  
  RESULTS
  Cefazolin and cefepime dialytic clearances were determined at blood and/or SPW flow rates of 100, 200, 300, and 400 ml/minute after a 15-minute equilibration period. The degree of correlation of in vitro and in vivo clearances with blood flow rate was determined. Cefepime dialytic clearance increased proportionally with blood flow rate (p<0.01), reaching a maximum mean +/- SD value of 178.9 +/- 24.3 ml/minute at a blood flow rate of 400 ml/minute. Cefazolin dialytic clearance ranged from a mean +/- SD of 42.3 +/- 7.7 to 52.7 +/- 16 ml/minute; no significant correlation was noted between blood flow rate and dialytic clearance. In vitro cefazolin and cefepime dialytic clearances increased proportionally with SPW flow rate (p<0.05). After adjusting the in vitro cefazolin and cefepime dialytic clearances based on their degrees of protein binding, the correlation between the in vitro and in vivo cefepime dialytic clearances was significant (r(2)=0.91, p=0.04), but no significant correlation was noted between the in vitro and in vivo cefazolin clearances (r(2)=0.61, p=0.22).
  
  
  CONCLUSIONS
  The in vivo hemodialysis clearances of cefepime and cefazolin with the new high-flux polysulfone dialyzer used in this study are markedly higher than values reported with conventional dialyzers but similar to values observed with other high-flux hemodialyzers. The in vivo dialytic clearance of cefazolin was significantly lower than the in vitro values, most likely due to cefazolin's high degree of protein binding. These results highlight the limitation of directly applying in vitro data to clinical situations.
authors.affiliation: Department of Clinical Pharmacy, West Virginia University School of Pharmacy, Morgantown, WV, USA.
authors.forename: Lena M
authors.initials: LM
authors.lastname: Maynor
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Carl
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matzke
authors.forename: Todd W B
authors.initials: TW
authors.lastname: Gehr
authors.forename: Christine
authors.initials: C
authors.lastname: Farthing
authors.forename: Don
authors.initials: D
authors.lastname: Farthing
authors.forename: Donald F
authors.initials: DF
authors.lastname: Brophy
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002437:Cefazolin / Q000493:pharmacokinetics*; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D002437:Cefazolin