Pharmacokinetics of intraperitoneal cefazolin and ceftazidime coadministered to CAPD patients.
OBJECTIVE
Guidelines for empiric treatment of PD-related peritonitis published in 2000 recommend concurrent intraperitoneal (IP) cefazolin and ceftazidime. The pharmacokinetics (PK) of these agents combined have not been studied. This study was designed to determine the PK of combined IP cefazolin and ceftazidime in CAPD patients.


METHODS
Prospective PK study in seven non-infected CAPD patients.


METHODS
Patients had a peritoneal equilibration test (PET), then received one IP dose of cefazolin and ceftazidime (15 mg/kg each) co-administered over a 4-hour dwell, then performed three CAPD exchanges over the next 16 hours. Serum and dialysate samples collected over the 20-hour study period were assayed for drug concentrations by HPLC.


METHODS
PK parameters.


METHODS
Correlations were tested between PET and PK parameters using the Pearson-product correlation coefficient.


RESULTS
Serum cefazolin and ceftazidime levels exceeded the minimum inhibitory concentrations for susceptible organisms (8 mg/L) throughout the 20 hour study period. Mean cefazolin and ceftazidime PK parameters included: bioavailability, 71% and 63%; elimination rate constant, 0.031 and 0.045 h -1 ; total clearance, 5.8 and 16.0 ml/min; peritoneal clearance, 1.6 and 3.9 ml/min; renal clearance, 2.3 and 3.9 ml/min, respectively. Predictive equations suggest that 1000 mg IP of cefazolin and of ceftazidime every 24 hours would produce average steady-state trough serum cefazolin and ceftazidime concentrations of 70 +/- 52 mg/L and 17 +/- 7 mg/L, respectively. There was no correlation between PET and PK parameters.


CONCLUSIONS
Co-administration did not adversely affect the PK of either agent. IP cefazolin and ceftazidime (15 mg/kg) produced adequate serum and dialysate concentrations in CAPD patients for 20 hours. PK predictions suggest that most patients would achieve adequate cefazolin and ceftazidime concentrations with 1000 mg IP once-daily. Anuric patients and those with significant residual renal function may require a more individualized approach.
Elwell
R J
RJ
Department of Pharmacy Practice, Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208, USA.
Manley
H J
HJ
Frye
R F
RF
Bailie
G R
GR
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002437:Cefazolin / Q000493:pharmacokinetics*; D002442:Ceftazidime / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000378:metabolism; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D002437:Cefazolin