The effect of combined fenofibrate and cholestyramine therapy on low-density lipoprotein kinetics in familial hypercholesterolemia patients

The effects of combined drug treatment (fenofibrate and cholestyramine) have been investigated in vivo by simultaneously determining total and receptor-independent LDL catabolism with 125I-labelled LDL and 131I-labelled LDL coupled with cyclohexanedione. Receptor-mediated catabolism of LDL determined as the difference between the turnover of 125I and 131I, was found to be reduced in heterozygotes with familial hypercholesterolemia. Treatment with combined fenofibrate and cholestyramine markedly stimulated both receptor-mediated (by more than 2-fold) and receptor-independent catabolism. LDL-Apo B and LDL-cholesterol levels were reduced by 38% and 36%, respectively. The combined treatment also reduced the absolute synthetic rate of LDL-Apo B (by 9%). The mechanisms responsible for these kinetic effects are discussed.