Clinical pharmacokinetics of bezafibrate in patients with impaired renal function

Abstract

The pharmacokinetics of the new lipid-lowering drug bezafibrate has been investigated in patients with impaired renal function and hyperlipoproteinaemia. 12 patients received a single oral dose of bezafibrate 300 mg. Plasma and urine samples were collected and bezafibrate was analyzed by gas chromatography. Eight of the patients had moderately impaired renal function, with a creatinine clearance between 20 and 40 ml/min; the mean plasma half-life of bezafibrate in them was 7.8 +3.9 h (SD) and the plasma clearance was 0.03 +0.02 1/kg . h. Three of the patients had a creatinine clearance greater than 40 ml/min; in them the plasma half-life was shorter, 4.6 +1.2 h, and the plasma clearance was higher, 0.06 +0.01 1/kg . h. The slowest elimination of bezafibrate was found in a patient with a creatinine clearance of only 13 ml/min. This patient had a plasma half-life of 20.l h, which is ten times longer than has been reported in healthy volunteers. Thus, when treating hyperlipoproteinaemia in patients with impaired renal function, the dosage of bezafibrate must be individualized because of its reduced renal elimination.