Influence of peritoneal dialysate flow rate on the pharmacokinetics of cefazolin.
OBJECTIVE
To determine the impact of dialysate flow rate (DFR) on cefazolin pharmacokinetics (PK) in peritoneal dialysis (PD) patients.


METHODS
A meta-analysis of published reports, identified by MEDLINE search (1966-2002) and other sources, containing information on cefazolin PK data in PD patients was conducted. Data were analyzed based upon low DFR (< or = 5.50 mL/minute) or high DFR (> 5.50 mL/minute). Data available were from North American (NA) (n = 45) and Singaporean (n = 10) patients. Complete data sets were available for 33 patients (CDS patients). Data were analyzed with respect to data origin and data set completeness: all patients (ALL), NA, and CDS. Analysis of log-transformed cefazolin PK data was performed to determine coefficient of determination (r2) between DFR and cefazolin elimination rate constant (kel), clearance total (ClT), and clearance peritoneal (ClPD). Clearance total data were extrapolated to DFR observed in continuous flow PD.


RESULTS
Published literature provided data on 55 PD patients (12 high DFR, 43 low DFR). Regardless of data origin (ALL, NA, or CDS), a prominent coefficient of determination (p < 0.0001) existed between DFR and all cefazolin PK data except ClPD. The p value for DFR correlation to ClPD was 0.953, 0.011, and 0.036 for ALL, NA, and CDS patients, respectively. Cefazolin ClT and ClPD increased at higher DFRs.


CONCLUSIONS
These findings demonstrate that an increased DFR leads to an increased rate of cefazolin clearance in NA PD patients. The impact of Asian descent on cefazolin ClPD warrants further investigation. Clinicians dosing cefazolin in PD patients using a higher DFR than that used to determine cefazolin PK should use increased doses or prescribe lower/comparable DFRs. Data are not yet available for patients prescribed very high DFRs (e.g., continuous flow PD); extrapolation of our results demonstrates significant influences on clearance and risk for underdosing.
Manley
Harold J
HJ
School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64108, USA. ManleyH@UMKC.edu
Bridwell
Darcie L
DL
Elwell
Rowland J
RJ
Bailie
George R
GR
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002437:Cefazolin / Q000493:pharmacokinetics*; D015314:Dialysis Solutions / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000379:methods*; D012212:Rheology
D000900:Anti-Bacterial Agents; D015314:Dialysis Solutions; D002437:Cefazolin