EFFECTS OF CIPROFIBRATE ON LDL METABOLISM IN MAN

This study examined the effects of ciprofibrate therapy (100 mg/day) o n plasma lipids, lipoproteins and low density lipoprotein (LDL) kineti c heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectiv ely. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high densit y lipoprotein (HDL) increased by 11%. LDL structural and metabolic het erogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II: and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). B aseline turnover studies revealed that LDL catabolism was subnormal an d this was the cause of the raised cholesterol in these subjects. Cipr ofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated t hat the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of an d hence reduced the plasma mass of apoLDL in the slowly metabolised po ol B. This perturbation in synthesis was linked to the change in plasm a triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL rec eptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metaboli sm of LDL.