Interaction of cyclosporin A with human lipoproteins

Abstract

The ultracentrifugal fractionation of human serum after previous incubation with cyclosporin A showed that, in healthy fasting individuals, 8% of cyclosporin A was found in the very low density lipoproteins (VLDL), 31% in the low density lipoproteins (LDL), 46% in the high density lipoproteins (HDL) and 15% in the non-lipoprotein protein fraction. In non-fasted, healthy and in non-fasted, lipaemic individuals, 7 and 6% of cyclosporin A was found in chylomicrons, 9 and 13% in VLDL, 28 and 30% in LDL, 39 and 37% in HDL, and 12 and 13% in the non-lipoprotein protein fraction, respectively. In patients receiving cyclosporin A the distribution varied from 12 to 19% in VLDL, 21 to 28% in LDL, 33 to 43% in HDL, and 13 to 20% in non-lipoprotein proteins. The interaction between cyclosporin A and isolated normal human lipoproteins was also studied by ultrafiltration. All lipoproteins exhibited a non-saturable, low affinity, high capacity uptake for cyclosporin A. Analysis of the uptake by phospholipid vesicles showed a similar uptake, suggesting that cyclosporin A dissolves in the lipophilic portion of the lipoprotein molecule rather than being associated with specific binding sites.

Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin

“…Albumin and lipoprotein binding account for 60 and 30% of the insecticide in adult human plasma (16). Cyclosporine the most highly lipophilic compound, associates largely with lipoproteins by partitioning into their nonpolar lipid core (9,21). In view of incomplete ontogeny data in the literature, it was deemed worthwhile to establish with greater certainty when plasma binding of each of the three compounds attained adult levels.…”

Effect of Serum Triglyceride Concentration on the Fluctuation of Whole Blood Concentration of Cyclosporin A in Patients.

“…[6][7][8] It was therefore considered that the fluctuation of CYA trough blood concentrations was deeply related to its distribution into them. In this study, the pharmacokinetics of CYA was next examined in rats with or without pseudo-hypertriglyceridemia, hypocythemia, and acute renal failure.…”

Tacrolimus, cyclosporine and plasma lipoproteins in renal transplant recipients

“…It is of interest to note, that Warty et al [31] reported that tacrolimus and CsA show significantly different binding and distribution among plasma lipoproteins and proteins. The majority of plasma CsA is associated with LDL and HDL, [12,22] where the average percent distribution of cholesterol is highest. Plasma tacrolimus, on the other hand, is mainly associated with plasma proteins, such as albumin and/or alpha-1 acid glycoprotein Abnormalities in circulating lipoproteins are common after renal transplantation, and they have been reported in the past [5,8,12,14,15,20,22,29].…”

“…The majority of plasma CsA is associated with LDL and HDL, [12,22] where the average percent distribution of cholesterol is highest. Plasma tacrolimus, on the other hand, is mainly associated with plasma proteins, such as albumin and/or alpha-1 acid glycoprotein Abnormalities in circulating lipoproteins are common after renal transplantation, and they have been reported in the past [5,8,12,14,15,20,22,29]. These abnormalities include elevations in total cholesterol, LDL cholesterol, apoB [17], as well as increases in VLDL and triglycerides.…”

“…Oxidation of LDL LDL samples were oxidized immediately after isolating, and each experiment consisted of 4 samples which include two controls [22]. Typically, 100 pglrnl of LDL was incubated in PBS with 5 pM copper ions.…”