a permanent indwelling Tenckhoff catheter in place. Patients were free of any signs of peritonitis and all other medications were continued in the usual manner during the study period. All attempts were made to continue the dialysis procedure in the same manner as that preceding the study. The dialyzing fluid for the study was 2-liter bags ofDianeal 1.5% dextrose. During the 24-hour study period, we scheduled the four dwell periods, i.e. , the time from instillation of fresh solution to drainage of the dialysate as follows: 0930-1400; 1430- 1900; 1930-2400 and 00300900 hours . Administration of Cimetidine: The study was initiated with the instillation of 2 liters of Dianeal -1.5% dextrose solution into the peritoneal cavity before the administration of cimetidine. All six patients received 300 mg of cimetidine diluted in 50 ml of normal saline intravenously over a 10-minute period. Three-ml blood samples were withdrawn from an intravenous cathe ter in the opposite arm. During the first dwell period, blood samples were taken at time 0 (beginning of the infusion), 10 minutes (end of the infusion), 1 hour, midpoint of the dwell (2 hours) and at the end of the dwell. At the end of the first and next three dwell periods, both blood and dialysate were collected. During the study, a total of eight three-ml blood samples were with drawn. The blood samples were centrifuged immediately, the plasma aspi rated and then stored frozen until the time of analysis. The total volume of the dialysate from each dwell was measured and an aliquot taken and frozen. Subsequently, we determined the concentration of cimetidine in plasma and dialysate, and the amount of drug removed during each dwell period. The details of the assay, sample presence of peritoneal dialysis solution i n the peritoneal cavity, except for brief periods of drainage and instillation of fresh solutions four times daily. Essentially, CAPD represents a continuous portable dialysis system. Renal failure patients reportedly have a higher incidence of peptic ulcer disease than the general population ( 4) , perhaps on the basis of gastric acid hypersecretion (5) and abnormal gas tric permeability (6). Cimetidine (Tag amet) , a histamine H2 receptor blocker , has become a useful therapeutic agent for this group of patients. Although it is associated with a low incidence of toxicity, it can induce mental confusion especially if the dosing rate is not reduced in renal failure (7, 8). The disposition of cimetidine has been studied in renal failure patients on hemodialysis (9, 10) and on peritoneal dialysis (10, II). We report our experience on the pharmaco- kinetics of cimetidine in patients on CAPD. SUBJECTS AND METHODS Six male patients, including two diabetics, with end-stage renal failure on CAPD were studied at Sunnybrook Medical Center. Their mean age was 62.2 ± 4.5 years (x ± SEM), and they had a mean weight of69.3 ± 2.6kg. At the time of the study the mean serum creatinine and BUN were 9.5 ± 0.84 mg/dl and 64.8 ± 4.7 mg/dl respectively. The creatinine clearance for these patients was between 1 and 3 ml/min. Patients were studied within one month of their initiation into the CAPD program. The study was ap - proved by the Human Ethics Commit tee, University of Toronto. Written informed consent was obtained from each patient before inclusion in the study. Dialysis Procedure: All patients had Thomas W. Paton M. Arifie Manuel and Scott E. Walker SUMMARY The disposition of cimetidine was studied following a single intravenous dose of 300 mg over 10 minutes in six male patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). The infusion of cimetidine and CAPD were initiated simultaneously. Cimetidine disappearance from plasma was biphasic with beta-phase ti varying from 6.1 to 7.4 hours. The total body clearance varied from 138 to 195 ml/min with a peritoneal clearance ranging from 1.9 to 4.0 ml/min. The total amount of cimetidine removed in the dialysate varied from 3.1 to 8.3 mg (1.2 to 2.7% of the dose administered) over 24 hours. This study demonstrates that very little cimetidine is removed by CAPD. We recommend that, to avoid toxicity, patients on CAPD should be given 200 mg cimetidine every 12 hours. Continuous ambulatory peritoneal dialysis (CAPD) has become an acceptable alternative to both hemodialysis and intermittent peritoneal dialysis (1-3). CAPD requires the continuous From the Department of Phannacy and Division of Nephrology , Department of Medicine, University of Toronto, Sunnybrook M edical Center, Toronto, Ontario, Canada. This work was presented at the 92nd Annual Meeting of the American Society for Clinical Phannacology and Therapeutics, New Orleans, March, 1981. This investigation was supported by grants from Smith, Kline and French, Canada Limited and by the Sunnybrook Trust Fund for Medical Research, Toronto, Ontario. CIMETIDINE DISPOSITION IN PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIAL YSIS by on July 21, 2011 www.pdiconnect.com Downloaded from