Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--.

The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral) and tacrolimus (TAC; Prograf) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C(2)) substituted for peak concentration (C(p)) and TAC at trough concentration (C(t)). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with C(p) and C(t) versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C(2) for CYA and C(t) for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, C(p), and C(t).

Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients.

ABO-incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti-A/B antibodies located on endothelial cells raises the risk of antibody-mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living-donor liver transplantation from ABO-incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long-term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO-incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody-mediated humoral rejection.