Distribution of fenofibric acid in lipoprotein fractions of patients.

The antidyslipidemic agent fenofibrate (procetofen) is hydrolysed in vivo to its main active metabolite--fenofibric (procetofenic) acid. This metabolite is usually determined in pharmacokinetic studies, because plasma concentrations of fenofibrate are practically undetectable. Presented study is focussed on the distribution of fenofibric acid into lipoprotein (VLDL, LDL, IDL and HDL) fractions of human and (for comparison) minipig blood plasma, which has not been studied yet. In order to obtain more accurate results, a new HPLC method based on the use of newly synthetized internal standards was developed. Four homologues of fenofibric acid prepared have identical chromophoric part of their molecules and hence the same UV spectra as fenofibric acid. From this point of view, these standards are more suitable for determination of fenofibric acid than the formerly used ones--naproxen or bezafibrate. Fenofibric acid levels in the high density lipoprotein fraction has been shown to be significantly higher (in both human and minipig plasma) than in the other lipoprotein fractions. This fact may be explained by higher affinity of the fenofibric acid to proteins constituting major part of the high density lipoprotein fraction.