Hepatic allograft cyclosporine concentration is independent of the route of cyclosporine administration and correlates with the occurrence of early cellular rejection.

This study compares the hepatic-tissue cyclosporine concentrations in liver biopsy specimens from patients with and without cellular rejection after orthotopic liver transplantation. Nine patients without cellular rejection were studied, including five patients receiving intravenous cyclosporine who had biopsies on posttransplant day 7 and four patients receiving oral cyclosporine who had biopsies on day 21. In these patients no significant differences were seen in blood cyclosporine concentrations (mean +/- S.D.) (310 +/- 162 vs. 273 +/- 310 ng/ml) and hepatic-tissue cyclosporine concentrations (3,451 +/- 1,262 vs. 3,545 +/- 456 ng/gm). These nine patients without cellular rejection were then compared with eight patients with cellular rejection who were receiving intravenous cyclosporine, including seven patients who had biopsies on post-transplant day 7 and one patient who had a biopsy on day 14. In patients with and without cellular rejection blood cyclosporine concentrations were 330 +/- 64 vs. 294 +/- 146 ng/ml, and hepatic-tissue cyclosporine concentrations were 1,879 +/- 998 vs. 3,493 +/- 936 ng/gm, p less than 0.01. We conclude that hepatic-tissue cyclosporine concentrations are independent of the route of cyclosporine administration and that low hepatic-tissue cyclosporine concentrations correlate with early cellular rejection after orthotopic liver transplantation.