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Clofibrate treatment of hyperlipidemia in chronic renal failure
Insights
Clofibrate, a hypolipidemic agent, shows prolonged half-life in patients with chronic renal failure. Careful monitoring ensures safe and effective treatment for hyperlipidemia in these patients.
Area of Science:
- Pharmacology
- Nephrology
- Clinical Therapeutics
Background:
- Hyperlipidemia is common in patients with chronic renal failure.
- Anuric patients on hemodialysis often have altered drug pharmacokinetics.
- The safety and efficacy of clofibrate in this population require investigation.
Purpose of the Study:
- To investigate the pharmacokinetics of clofibrate in anuric patients undergoing hemodialysis.
- To evaluate the safety and efficacy of clofibrate for treating hyperlipidemia in chronic renal failure.
Main Methods:
- Single-dose pharmacokinetic study in healthy volunteers and uremic patients.
- Maintenance dose administration and monitoring for myotoxicity.
- Assessment of lipid-lowering effects over a 3-month period.
Main Results:
- Clofibrate exhibited a significantly prolonged plasma half-life in uremic patients compared to healthy controls (68.4 hr vs. 16.7 hr).
- Myotoxicity was observed at plasma levels considered safe in patients with normal renal function, necessitating careful monitoring.
- Significant reductions in serum total lipid, triglyceride, and cholesterol levels were achieved.
Conclusions:
- Clofibrate treatment for hyperlipidemia in uremic patients is safe and efficacious when carefully monitored.
- The altered pharmacokinetics in renal failure patients necessitate dose adjustments and vigilant safety monitoring.
- Sustained lipid reduction was observed in some patients post-treatment.
Abstract:
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.