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 (CLT) was 31.29 ± 6.02 mL/minute. Renal CL (CLR) and PD CL (CLPD) accounted for 8.8% and 16.8% of CLT; CLR correlated well with GFR (CLR = 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.

Automated Peritoneal Dialysis Symposium: Treatment of Peritonitis in APD: Pharmacokinetic Principles

“…To date, only cefazolin, tobramycin, vancomycin, piperacillin, and fluconazole pharmacokinetics studies in APD patients have been published (7)(8)(9)(10). With the exception of fluconazole, the methodology employed by the investigators was the same for each antibiotic (7-9).…”

“…To date, only cefazolin, tobramycin, vancomycin, piperacillin, and fluconazole pharmacokinetics studies in APD patients have been published (7–10). With the exception of fluconazole, the methodology employed by the investigators was the same for each antibiotic (7–9). Briefly, 8–10 patients were recruited and received a single dose of an antibiotic just prior to a cycler regimen being performed.…”

“…The importance of RRF on antibiotic clearance was identified in all studies. Antibiotic renal clearance correlated significantly with residual function for cefazolin (7) ( r 2 = 36%, p = 0.05); tobramycin (7) ( r 2 = 52%, p < 0.005); vancomycin (8) (renal clearance = 0.90 GFR − 1.01, r 2 = 0.79, p = 0.008); piperacillin (9) (renal clearance = 0.86 GFR + 0.1, p < 0.00003); and fluconazole (10) ( r 2 = 0.98, p not provided). These results are similar to those reported in CAPD patients.…”

“…Clinicians treating peritonitis should be made aware of the differences in antibiotic disposition between CAPD and APD patients. Several reports have demonstrated that peritoneal clearance of antibiotics is different in CAPD and APD (7–10). We herein review the literature and compare the effects of APD to those of CAPD on various antibiotic peritoneal pharmacokinetic (PK) parameters.…”

Pharmacokinetics and safety of oseltamivir in patients with end‐stage renal disease treated with automated peritoneal dialysis

“…Patients were converted to a standardized, broadly applicable APD regimen comprising three CCPD exchanges (3 × 2.5 litres) over an 8 h period during the day and two CAPD sessions (2 × 2.0 litres) over 16 h overnight (Supplementary Figure S1). This regimen had previously been used successfully [15] and is in alignment with The National Kidney Foundation guidelines for effective peritoneal dialysis [14]. Dextrose (1.5-4.25% w/v) was used for all exchanges over 24 h except for one 8 h CAPD exchange, in which icodextrin 7.5% w/v was the osmotic agent.…”