Effects of bezafibrate on receptor-mediated and receptor-independent low density lipoprotein catabolism in type II hyperlipoproteinaemic subjects.

This study examines the effects of bezafibrate (200 mg t.i.d.) on LDL metabolism in 7 type II hyperlipoproteinaemic subjects. Eight weeks of treatment lowered plasma cholesterol and triglyceride by 10% and 30%, respectively (P less than 0.02). These reductions were associated with a fall in circulating VLDL (31%, P less than 0.02) and LDL (11%, P less than 0.05), while HDL cholesterol stayed the same. LDL metabolism changed during therapy. The plasma fractional clearance rate (FCR) of autologous [125I]LDL normalized from a low value of 0.256 +/- 0.048 (mean +/- SD) to 0.298 +/- 0.040 pools/day (P less than 0.001). This was attributable to a 65% increase (P less than 0.01) in receptor-mediated LDL catabolism since the clearance of simultaneously injected 1,2-cyclohexanedione-modified [131I]LDL, which measures the receptor-independent pathway, was unaltered (FCR of [131I]cyclohexanedione/LDL in control phase = 0.194 +/- 0.030 pools/day; during drug treatment = 0.194 +/- 0.024 pools/day). We conclude that bezafibrate lowers plasma LDL in type II hyperlipoproteinaemia by promoting its degradation via high affinity receptors.