The pharmacokinetics of the
hypolipidemic agent,
clofibrate have been studied in anuric patients on intermittent
hemodialysis. In addition we have tried to determine whether the treatment of
hyperlipidemia of
chronic renal failure with
clofibrate was safe and efficacious. Seven healthy volunteers and five uremic patients received a single dose of 25 mg/kg
body weight of
clofibrate. Mean peak plasma levels of
clofibrate were comparable in both groups and were reached 3.5 hr after
drug ingestion in the control subjects and after 6.5 hr in the uremic patients. The mean plasma half-life of
clofibrate was 16.7 hr and 68.4 hr in the control subjects and in the patients, respectively (P less than 0.001). Following a short loading period a daily oral maintenance dose of 5 mg/kg
body weight was given leading to a plasma
clofibrate level of 75-100 microgram/100 ml. Five hyperlipidemic uremic patients received this dose for 3 months. Their plasma
clofibrate and
creatine kinase levels were constantly monitoried to detect
clofibrate myotoxicity which we have observed in uremic patients at plasma levels generally considered safe in patients with normal renal function. Significant decreases in serum total
lipid,
triglyceride, and
cholesterol levels were observed when compared to pretreatment values. In two of the 5 patients serum
lipids remained decreased for 10 and 14 months. It is concluded that
clofibrate treatment of
hyperlipidemia in uremic patients, when carefully monitored, is safe and efficacious.