Gardier A M, Mathé D, Guédeney X, Barré J, Benvenutti C, Navarro N, Vernillet L, Loisance D, Cachera J P, Jacotot B
Laboratoire hospital-universitaire de Pharmacologie, Centre hospitalier intercommunal, Créteil, France.
Ther Drug Monit. 1993 Aug;15(4):274-80. doi: 10.1097/00007691-199308000-00003.
The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol--TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.
本研究试图描述等待心脏移植患者血浆中环孢素A（CsA）在脂蛋白组分（分别为极低密度脂蛋白、中间密度脂蛋白、低密度脂蛋白和高密度脂蛋白，即VLDL、IDL、LDL和HDL）中的分布情况，以及血浆脂质成分对CsA药代动力学的影响。治疗浓度的CsA主要分布在HDL和LDL中。此外，血浆脂质浓度（分别为总胆固醇、甘油三酯、磷脂、极低密度脂蛋白胆固醇——TC、TG、PL、VLDLc）与CsA在LDL组分中的分布呈正相关，与CsA在HDL组分中的分布呈负相关。因此，每种脂蛋白中CsA的百分比显示会因个体脂质水平而异。在血浆中稳态表观分布容积（Vss）与TC、PL和LDLc之间以及全血血药浓度-时间曲线下面积（AUCB）与PL之间发现显著负相关。
