Evaluation of the pharmacodynamic profile of commonly used intravenous vancomycin dosing schemes in patients on automated peritoneal dialysis.
OBJECTIVE
The intent of this study was to evaluate the appropriateness of commonly used intravenous (iv) vancomycin dosing schemes in patients on automated peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and Monte Carlo simulation.


METHODS
Data from a single-dose PK study of 10 non-infected APD patients ≥18 years old were analysed. Patients received iv vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h, followed by two 8 h dwells. Serum and dialysate samples were collected over the entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte Carlo simulation was used to determine the probability of achieving an AUC/MIC ratio of >400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h).


RESULTS
In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred >90% probability of achieving an AUC/MIC ratio of >400 for MIC values <2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations >20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L.


CONCLUSIONS
Although expert guidelines suggest iv vancomycin may be an acceptable empirical therapy for patients on APD with infection, these analyses indicate that iv vancomycin may not be effective for peritonitis but may be a viable option for non-peritoneal infections with MIC values ≤1 mg/L.
Albany College of Pharmacy and Health Sciences, Albany, NY, USA katie.cardone@acphs.edu.
Katie E
KE
Cardone
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Wen Zhen
WZ
Chen
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Darren W
DW
Grabe
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Amber
A
Batzold
Dialysis Clinic Inc., Albany, NY, USA.
Harold J
HJ
Manley
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Thomas P
TP
Lodise
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015233:Models, Statistical; D010530:Peritoneal Dialysis; D044967:Serum / Q000737:chemistry; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
D000900:Anti-Bacterial Agents; D015314:Dialysis Solutions; D014640:Vancomycin
Monte Carlo simulation; antibiotics; peritonitis; pharmacokinetics