Experience with Neoral versus Sandimmune in primary liver transplant recipients

Abstract

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 +/- 1.9 days in the Neoral group vs 7.8 +/- 4.9 days in the Sandimmune group. (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13%) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year post-transplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70% using Sandimmune.

An Evaluation of Combined Immunosuppression with MNA 715 and Microemulsified Cyclosporine on Renal Allograft Rejection in Mismatched Mongrel Dogs

“…In human transplant patients, the use of microemulsified cyclosporine reduced the number of rejection episodes compared with the oil‐based formulation in renal allografts (35% v 50% to 60%) and liver transplants (24% v . 70%) 47,48 . In dogs, the pharmacokinetics of oil‐based cyclosporine and efficacy of this formulation to prevent renal allograft rejection have been reported, 8,9,12,49 but to the authors' knowledge, there are no similar reports on microemulsified cyclosporine.…”

“…46 In human transplant patients, the use of microemulsified cyclosporine reduced the number of rejection episodes compared with the oil-based formulation in renal allografts (35% v 50% to 60%) and liver transplants (24% v. 70%). 47,48 In dogs, the pharmacokinetics of oil-based cyclosporine and efficacy of this formulation to prevent renal allograft rejection have been reported, 8,9,12,49 but to the authors' knowledge, there are no similar reports on microemulsified cyclosporine. The improved intestinal absorption and increased bioavailability of microemulsified cyclosporine may ex-plain the improved renal allograft survival in mismatched dogs observed in this study compared with previous reports using oil-based cyclosporine.…”

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

“…In particular, younger children and children with Roux-en-Y biliary anastomosis or cholestasis showed more consistent drug absorption with Neoral (48-50). Studies using Neoral have shown a reduced incidence of rejection as compared with Sandimmune in liver recipients, with no significant difference in toxicity (51)(52)(53).…”

Immunosuppression in Liver Transplantation

“…27 Studies using Neoral have shown a reduced incidence of rejection as compared with Sandimmune CsA in liver recipients, with no significant difference in toxicity. [28][29][30] Recent pharmokinetic studies of Neoral have shown that the absorption phase (0-4 hrs) has the greatest individual variability. Furthermore, the blood concentration of cyclosporin 2 hours after oral ingestion (C 2 ) correlated better with AUC than the commonly measured trough concentration (C 0 ).…”