Pharmacokinetic modeling of bidirectional transfer during peritoneal dialysis

A pharmacokinetic model and distributional clearance terms to describe bidirectional peritoneal transfer were used to examine cefamandole pharmacokinetics in five uninfected patients with end-stage renal disease who were receiving continuous ambulatory peritoneal dialysis. Each patient received intravenous and intraperitoneal 1 gm doses of drug, and serum and dialysate samples were collected over three dialysis dwell periods. The mean systemic availability of cefamandole after intraperitoneal dosing was 0.71 +/- 0.1. No significant differences in the serum-to-peritoneal fluid and peritoneal fluid-to-serum distributional clearances were observed. The time dependence of peritoneal dialysis clearance was examined. The amount of drug found in the dialysate divided by the corresponding serum AUC was empirically found to estimate the time-averaged peritoneal dialysis clearance. A mass balance-area method to calculate distributional clearance was developed that obviates more complicated computer fitting of the data. We present a comprehensive modeling approach that should be useful in the examination of the kinetics of drugs during continuous ambulatory peritoneal dialysis.