Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients

Background: Use of intermittent antibiotic dosing is increasing in the trea tment of peritoneal dialysis (PD)related peritonitis. We studied the pharma cokinetics of intravenous (IV) piperacillin in automated PD patients. Patients and Methods: Eight patients (3 males, 5 females) were recruited an d received a single IV dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and en d of dwells 1 - 3 (on cycler), and end of dwells 4 - 5 (off cycler) for a 2 4-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a on e-compartment model. Glomerular filtration rate (GFR) and piperacillin clea rance (CL) values were normalized to 1.73 m(2). 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 ti mes 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 ton cycler 1.99 +/- 0.39 hr, off cycler 4.39 +/- 5.4 hr; p = 0.12) and rem ained insignificant, even accounting for an outlier ton cycler 2.01 +/- 0.4 1 hr, off cycler 2.54 +/- 1.48 hr; p = 0.19). Piperacillin total CL (CLT) w as 31.29 +/- 6.02 mL/minute, Renal Ct (CLR) and PD Ct (CLPD) accounted for 8.8% and 16.8% of CLT CLR correlated well with GFR (CL, = 0.86 GFR + 0.1; p < 0.000 03). Mean piperacillin serum and dialysate end-of-dwell concentrat ions were above minimum inhibitory concentration of susceptible organisms ( 8 <mu>g/mL) for the three cycler exchanges only. Serum and dialysate concen trations predicted using a one-compartment model suggest that IV piperacill in 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. Conclusion: The current IV piperacillin dosing recommendations of 4000 mg e very 12 hours for PD-related peritonitis are appropriate for patients on au tomated PD. Intermittent intraperitoneal piperacillin is not recommended.