Effect of Liver Regeneration on the Pharmacokinetics of Immunosuppressive Drugs

In liver transplantation the graft has been known to undergo regeneration, which is associated with down-regulation of the cytochrome P450 system. The latter is involved in the metabolism of several immunosuppressive drugs. The aim of this study was to investigate the effect of liver regeneration on the pharmacokinetics (PK) of cyclosporine, rapamycin, and tacrolimus. Rats were subjected to either partial hepatectomy (PH) or sham operation (SH). Cyclosporine, rapamycin, and tacrolimus PK studies were performed at 0, 24, and 96 hours postoperatively. The areas under the curve (AUC), trough levels, and maximum concentrations (Cmax) for cyclosporine and tacrolimus were numerically higher in the animals subjected to PH. The PK studies of rapamycin were not affected by PH. These studies indicated that cyclosporine and tacrolimus metabolism may be inhibited during liver regeneration.