Galli C, Sirtori C R, Mosconi C, Medini L, Gianfranceschi G, Vaccarino V, Scolastico C
Institute of Pharmacological Sciences, School of Sciences, University of Milan, Italy.
Lipids. 1992 Dec;27(12):1005-12. doi: 10.1007/BF02535580.
The plasma kinetics of a preparation of dilinoleoyl phosphatidylcholine (DLPC) specifically labeled with 3H in the choline moiety and with 14C in the 2-fatty acid (FA) were evaluated in six healthy volunteers after oral administration. Retention of both isotopes in plasma exceeded expectations, with a half-life in the elimination phase of 172.2 h for 3H and 69.7 h for 14C. Up to 60 d after administration, there were still significant levels of radioactivity present in plasma. The relative stability of the [14C]FA label was demonstrated by the retention for more than 12 h of an isotope ratio close to that of the compound administered. The 14C label of DLPC remained in position-2, as assessed by cleavage of plasma phospholipids with phospholipase A2. The [3H]choline label showed an early incorporation into high density lipoproteins and subsequently into low density lipoproteins (LDL); conversely, the 14C radioactivity was rapidly incorporated into triacylglycerols that were mainly associated with very low density lipoproteins. Radioactivity measurements revealed that both isotopes remained the longest time in LDL. In red blood cell (RBC) lipids, [3H]choline radioactivity accumulated over time, with a plateau after 48 h, whereas FA radioactivity accumulated more rapidly and was followed by a progressive decay. Analysis of the isotope ratio in these cells suggested an early incorporation of lyso products followed by rapid transfer of FA from plasma. The RBC maintained considerable radioactivity for a prolonged time, thus acting as a possible reservoir for the DLPC administered.(ABSTRACT TRUNCATED AT 250 WORDS)
在六名健康志愿者口服给予胆碱部分用³H特异性标记、2-脂肪酸(FA)用¹⁴C特异性标记的二亚油酰磷脂酰胆碱(DLPC)制剂后,评估了其血浆动力学。两种同位素在血浆中的滞留时间超过预期,³H在消除相的半衰期为172.2小时,¹⁴C为69.7小时。给药后长达60天,血浆中仍存在显著水平的放射性。[¹⁴C]FA标记的相对稳定性通过同位素比率在超过12小时内保持接近给药化合物的比率得以证明。通过用磷脂酶A2裂解血浆磷脂评估,DLPC的¹⁴C标记保留在2位。[³H]胆碱标记早期掺入高密度脂蛋白,随后掺入低密度脂蛋白(LDL);相反,¹⁴C放射性迅速掺入主要与极低密度脂蛋白相关的三酰甘油中。放射性测量显示两种同位素在LDL中停留的时间最长。在红细胞(RBC)脂质中,[³H]胆碱放射性随时间积累,48小时后达到平台期,而FA放射性积累更快,随后逐渐衰减。对这些细胞中同位素比率的分析表明,溶血产物早期掺入,随后FA从血浆中快速转移。红细胞在较长时间内保持相当水平的放射性,因此可能作为所给予DLPC的一个储存库。(摘要截断于250字)