Intraperitoneal and intravenous cefoperazone kinetics during continuous ambulatory peritoneal dialysis

Abstract

Serum cefoperazone (CFP) kinetics after a 1-gm dose added to the peritoneal dialysate were followed in seven patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In a randomized order five of the seven patients received 1 gm IV CFP. Serum samples were collected over 10 hr during one dialysate exchange interval. CFP concentrations were determined by HPLC. After intravenous dosing CFP mean peak and 6-hr serum concentrations were 104.2 +/- 29.1 micrograms X ml-1 and 8.5 +/- 3.8 micrograms X ml-1, mean body clearance was 80 +/- 20 ml X min-1, and mean apparent volume of distribution was 14.6 +/- 3.2 l. The elimination rate constant (kel) varied from 0.29 to 0.38 hr-1 and was almost identical to kel derived from intraperitoneal application (range 0.29 to 0.42 hr-1). Instillation of CFP with the peritoneal dialysate resulted in a rapid rise of serum levels (Tmax = 1.9 +/- 0.7 hr; absorption rate constant ka = 0.68 +/- 0.11 hr-1), and sufficient CFP concentrations (Cmax = 33.2 +/- 5.3 micrograms X ml-1), were maintained over 6 hr (C6 hr = 17.3 +/- 5.8 micrograms X ml-1). Mean systemic availability of intraperitoneal CFP was 95% +/- 12%. Intraperitoneal administration of CFP in patients undergoing CAPD resulted in serum levels of CFP adequate for systemic treatment of bacterial infections.