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Lipid lowering treatment with bezafibrate in patients on chronic haemodialysis: pharmacokinetics and effects
Insights
Bezafibrate effectively lowers lipids in chronic haemodialysis patients, despite altered pharmacokinetics. This study shows bezafibrate (BF) can reduce triglycerides and cholesterol in patients with hyperlipidaemia on chronic haemodialysis (CHD).
Area of Science:
- Nephrology and Cardiovascular Medicine
- Clinical Pharmacology
Background:
- Hyperlipidaemia is a significant risk factor for cardiovascular complications in patients undergoing chronic haemodialysis (CHD).
- Current lipid-lowering therapy options for CHD patients are limited, necessitating investigation into alternative treatments.
Purpose of the Study:
- To evaluate the efficacy and pharmacokinetics of bezafibrate (BF), a clofibrate analogue, in lowering lipids in patients with hyperlipidaemia on CHD.
- To assess the safety and long-term effects of bezafibrate therapy in this patient population.
Main Methods:
- A 6-month placebo-controlled trial involving 19 CHD patients with elevated triglycerides and/or total cholesterol (>300 mg/dl).
- Pharmacokinetic analysis of bezafibrate, including elimination half-life and serum concentration, after single and multiple doses.
- Long-term follow-up of six patients for a mean of 29 months.
Main Results:
- Bezafibrate significantly reduced serum triglycerides by 31% (from 478 mg/dl) and total cholesterol by 19% (from 311 mg/dl).
- Beta-lipoprotein cholesterol decreased by 17%, while alpha-lipoprotein cholesterol increased by 58%.
- Elimination half-life of bezafibrate was prolonged in CHD patients (17-22 h) compared to healthy subjects (2 h), necessitating dose adjustment to 200 mg every 3rd day.
Conclusions:
- Bezafibrate demonstrates significant lipid-lowering efficacy in patients with hyperlipidaemia on chronic haemodialysis.
- Altered pharmacokinetics in CHD patients require dose modification, but therapeutic serum concentrations can be achieved.
- Bezafibrate represents a viable therapeutic option for managing dyslipidaemia in patients undergoing chronic haemodialysis.
Abstract:
Hyperlipidaemia may contribute to the high rate of cardiovascular complications in patients on chronic haemodialysis (CHD). However, possibilities of lipid lowering therapy in CHD are still limited. The applicability of bezafibrate (BF), a recently developed clofibrate analogue, was investigated in patients on CHD with triglyceride and/or total cholesterol levels above 300 mg/dl. The lipid lowering effect was studied in a placebo-controlled trial over 6 months in 19 patients. Long-term effect was followed in six patients over a mean period of 29 months. Elimination half-life and mean therapeutic serum concentration were calculated by 72-h BF serum profiles, obtained after the first drug administration of a single 200-mg dose and during steady state after 12 weeks of treatment. Elimination half-lives were 17 h at start and 22 h after 12 weeks compared with 2 h in subjects with normal renal function. Dose reduction to 200 mg every 3rd day was necessary and resulted in a mean therapeutic serum concentration of 3.4 mg/l, which was similar to 3.0 mg/l of normal subjects, who received the dose optimal for lowering of lipids (200 mg 3 X/day). The protein-bound serum fraction of BF was decreased to 8% in CHD patients, compared with 95% found in normal subjects. BF therapy resulted in a marked reduction of serum triglycerides from 478 mg/dl by 31% and total cholesterol levels from 311 mg/dl by 19% as well as beta-Lp-cholesterol from 178 mg/dl by 17%, whereas the initially low alpha-Lp-cholesterol increased significantly from 18.3 mg/dl by 58%.(ABSTRACT TRUNCATED AT 250 WORDS)