Intermittent Intravenous Piperacillin Pharmacokinetics in Automated Peritoneal Dialysis Patients

Abstract

Background

Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (IV) piperacillin in automated PD patients.

Patients and Methods

Eight patients (3 males, 5 females) were recruited and received a single IV dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on cycler), and end of dwells 4 – 5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m².

Results

The patients were 49.5 ± 10.1 years of age (mean ± SD) and had been receiving PD for a median of 3 months (range 2 – 66 months). Dwell times were 2.25 ± 0.06 hours on cycler and 7.26 ± 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 ± 0.39 hr, off cycler 4.39 ± 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 ± 0.41 hr, off cycler 2.54 ± 1.48 hr; p = 0.19). Piperacillin total CL (CL_T) was 31.29 ± 6.02 mL/minute. Renal CL (CL_R) and PD CL (CL_PD) accounted for 8.8% and 16.8% of CL_T; CL_R correlated well with GFR (CL_R = 0.86 GFR + 0.1; p < 0.000 03). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 μg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that IV piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period.

Conclusion

The current IV piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.