The binding of two dihydropyridines to isolated and native plasma lipoproteins

The objectives of this study were to investigate the mechanisms involved in the interaction of two calcium antagonists, isradipine and amlodipine, with isolated lipoprotein fractions in-vitro and to determine the distribution of isradipine among individual plasma lipoproteins ex-vivo in healthy volunteers (n = 8) and in hypercholesterolaemic patients (n = 12). The total binding affinity of isradipine to isolated low density lipoprotein (LDL) was markedly higher compared with amlodipine; total binding affinity (nKa) of isradipine vs amlodipine was 1·60 ± 0·08 times 107 vs 4·14 ± 0·33 times 106m-1, respectively. Binding to high density lipoprotein (HDL) was also higher with isradipine, nKa = 1·04 ± 0·04 times 105m−1, compared with that of amlodipine, nKa = 3·82 ± 0·18 times 104m−1. The distribution study ex-vivo demonstrated the different relative affinity of isradipine for the plasma lipoproteins: HDL > LDL > very-low density lipoprotein (VLDL). Isradipine binding correlated linearly with the cholesterol levels in LDL and VLDL; however, binding to HDL did not correlate with the cholesterol level in this fraction. There was no significant competitive binding effect of cyclosporin A (1–5 μgmL−1) on isradipine binding to individual lipoprotein fractions. It is likely that, in addition to the structure of surface apoproteins, the factors determining the interaction of calcium antagonists with plasma lipoproteins also include the plasma level of each lipoprotein fraction as well as the lipophilicity of the drug.