EFFECTS OF FLUVASTATIN (XU-62-320), AN HMG-COA REDUCTASE INHIBITOR, ON THE DISTRIBUTION AND COMPOSITION OF LOW-DENSITY-LIPOPROTEIN SUBSPECIES IN HUMANS

We studied the effect of fluvastatin (XU 62-320), a new HMG-CoA reductase inhibitor, on the distribution of low density lipoprotein (LDL) subspecies and composition in humans. As expected, fluvastatin significantly lowered serum LDL levels (25% after 6 weeks of therapy). In addition, treatment with fluvastatin changed the LDL subspecies. In the group treated with fluvastatin, 38.5% of the individuals showed changes in the shape of LDL absorbance profile obtained from density gradient ultracentrifugation and 54% of the group showed changes in the electrophoretic mobility of the LDL bands. Of those showing changes in electrophoretic mobility, the majority (78%) shifted to slightly larger, less dense LDL after drug therapy. However, the LDL-cholesterol/apo B ratio changes were relatively small in all fluvastatin-treated individuals including the group with changes in eletrophoretic mobility, confirming that HMG-CoA reductase inhibitor causes relatively small and subtle changes in the distribution of LDL subspecies.