FOSINOPRIL PHARMACOKINETICS AND PHARMACODYNAMICS IN CHRONIC AMBULATORY PERITONEAL-DIALYSIS PATIENTS

The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, C(max), t(max), and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng.ml-1, 4.8 h, and 3.19-mu-g.h.ml-1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, C(max) of 182 ng.ml-1, t(max) of 9 h, and AUC of 18.1-mu-g.h.ml-1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml.min-1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.