PHARMACOKINETICS OF INTRAVENOUS AND INTRAPERITONEAL CEFTAZIDIME IN CHRONIC AMBULATORY PERITONEAL-DIALYSIS

The pharmacokinetics of ceftazidime have been investigated in eight pa tients with chronic renal failure undergoing continuous ambulatory per itoneal dialysis. Each subject was given ceftazidime 1 g intravenously and 1 g intraperitoneally at an interval of 1 week. Ceftazidime was a ssayed by high-pressure liquid chromatography. After intravenous admin istration, the pharmacokinetic parameters of ceftazidime were: elimina tion plasma half-life (t1/2beta) = 24.6 +/- 4.6 hours; apparent volume of distribution (V(area)): 0.37 +/- 0.09 1/kg, total plasma clearance (CL): 11.9 +/- 3.3 mL/minute, peritoneal clearance (CL(p)): 1.7 +/- 0 .3 mL/minute. Over 72 hours, only 15.6 +/- 4.7% of the dose was elimin ated by the peritoneal route. After intraperitoneal administration, ce ftazidime appeared in the plasma rapidly, and the peak plasma concentr ation of 24.5 +/- 5.2 mg/L was achieved at the fourth hour; the elimin ation half-life (t1/2ke) was 20.8 +/- 1.7 hours. The absorption of cef tazidime from the peritoneal space was 74.1 +/- 7.4%. These data sugge st that ceftazidime has bidirectional exchange characteristics through the peritoneal membrane. A single 1-g intraperitoneal dose led to ser um and dialysate concentrations of ceftazidime above the minimum conce ntrations for susceptible pathogen germs for 24 hours.