title: Pharmacokinetics of intermittent intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients.
abstract: OBJECTIVE
  To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients.
  
  
  METHODS
  Prospective nonrandomized open study.
  
  
  METHODS
  CAPD outpatient clinic in Albany, New York.
  
  
  METHODS
  Seven volunteer CAPD patients without peritonitis. Three of the patients were nonanuric while 4 were anuric.
  
  
  METHODS
  Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1,2,3,6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period.
  
  
  RESULTS
  The mean+/-SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7%+/-8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21+/-0.1/hr (absorption half-life 3.5+/-0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4+/-3.7 mg/L and 30.3+/-5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1+/-3.4 mg/L and 7.9+/-1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02+/-0.01/hr (elimination half-life 31.5+/-8.8 hr). The total cefazolin body clearance was 3.4+/-0.6 ml/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6+/-0.4 ml/min. The peritoneal clearance of cefazolin was 1.0+/-0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2+/-0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group.
  
  
  CONCLUSIONS
  A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.
authors: Albany College of Pharmacy, New York 12208, USA.
authors: H J
authors: HJ
authors: Manley
authors: G R
authors: GR
authors: Bailie
authors: R D
authors: RD
authors: Asher
authors: G
authors: G
authors: Eisele
authors: R F
authors: RF
authors: Frye
mesh_terms: D000042:Absorption; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D001002:Anuria / Q000378:metabolism; D002437:Cefazolin / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D015314:Dialysis Solutions / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000378:metabolism; D011446:Prospective Studies; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D002511:Cephalosporins; D015314:Dialysis Solutions; D002437:Cefazolin