Effect of plasma lipid on pharmacokinetics of ciclosporin and its relationship with plasma prednisolone level in renal transplant patients

Abstract

Ciclosporin (cyclosporine A, CyA) is a potent immunosuppressant used after organ transplantation. The pharmacokinetic properties of CyA vary widely and lipoproteins are the major complexing constituents for CyA in the plasma. Therefore, a change in lipoprotein level may influence the pharmacokinetic properties of CyA. Prednisolone (PSL) is concomitantly used with CyA as an immunosuppressant. After organ transplantation, hyperlipidaemia resulting from PSL therapy has been mostly observed and PSL increased the plasma lipoprotein level. Therefore, in this study, to obtain more useful information of the therapeutic drug monitoring (TDM) of CyA, the relationship between the plasma PSL level, plasma lipoprotein level and blood CyA level was investigated in detail. An open-label, non-randomized, retrospective study was performed. Data from 21 male and 11 female patients (age 11–65 years) who received a living-related renal transplantation from 2002 to 2004 were included. On postoperative days (PODs) 7, 14 and 28, the area under the plasma concentration-time curve until 9 h after 40 mg of PSL administration (AUCPSL400–9) correlated well with total cholesterol (T-cho) (r = 0.558, 0.768, 0.660, all P < 0.05) and high-density lipoprotein (HDL) (r = 0.688, P < 0.05; 0.835, P < 0.01; 0.508, P < 0.05), and correlated negatively with very-low-density lipoprotein (VLDL) (r = −0.486, P < 0.01; −0.776, P < 0.01; −0.967, P < 0.01). In addition, AUC until 9 h after CyA administration (AUCCyA0–9) also correlated with T-cho (r = 0.797, P < 0.01; 0.577, P < 0.05; 0.901, P < 0.01), HDL (r = 0.514, P < 0.05; 0.614, P < 0.05; 0.893, P < 0.01) and low-density lipoprotein (LDL) (r = 0.906, P < 0.01; 0.573, P < 0.05; 0.537, P < 0.05), and there was a negative correlation with VLDL (r = −0.480, −0.630, −0.632, all P < 0.05). Moreover, AUCCyA0–9 correlated well with AUCPSL400–9 (r = 0.728, P < 0.01; 0.482, P < 0.05; 0.688, P < 0.05); namely, it was considered that the variety of plasma PSL concentrations influenced the pharmacokinetic properties of CyA through the change in lipoprotein levels. These results suggested that monitoring of the biochemical parameters of the plasma lipid and plasma PSL level might be useful for the TDM of CyA.