Nobilis M, Kvetina J, Anzenbacher P, Vontor T, Svoboda D, Brátová M, Solichová D, Zadák Z, Bláha V, Vlcek J
Institute of Experimental Biopharmaceutics, Joint Research Center of Academy of Sciences of the Czech Republic and PRO.MED.CS.Praha a.s., Hradec Králové.
Eur J Drug Metab Pharmacokinet. 1998 Apr-Jun;23(2):287-94. doi: 10.1007/BF03189353.
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.
抗血脂药非诺贝特（丙贝酸）在体内水解为其主要活性代谢产物——非诺贝特酸（丙贝洛芬酸）。在药代动力学研究中通常测定这种代谢产物，因为非诺贝特的血浆浓度实际上难以检测到。本研究聚焦于非诺贝特酸在人血浆以及（作为对照）小型猪血浆的脂蛋白（极低密度脂蛋白、低密度脂蛋白、中间密度脂蛋白和高密度脂蛋白）组分中的分布情况，这方面尚未有研究。为了获得更准确的结果，开发了一种基于使用新合成内标的高效液相色谱新方法。所制备的四种非诺贝特酸同系物具有相同的分子发色部分，因此与非诺贝特酸具有相同的紫外光谱。从这一角度来看，这些标准品比以前使用的萘普生或苯扎贝特更适合用于测定非诺贝特酸。已表明高密度脂蛋白组分中的非诺贝特酸水平（在人血浆和小型猪血浆中）显著高于其他脂蛋白组分。这一事实可能是由于非诺贝特酸对构成高密度脂蛋白组分主要部分的蛋白质具有更高的亲和力。
