Comparison of Absorption Profile between Microemulsion and Non-microemulsion Cyclosporine in Stable Renal Transplant Recipients and Therapeutic Drug Monitoring

Abstract

Background: Cyclosporine has a narrow therapeutic window and many serious side effects. The new oral microemulsion cyclosporine is known to have better absorption profile than non-microemulsion cyclosporine. The purpose of this study was to confirm above finding in stable renal transplant patients and also to compare correlation between AUC_(0-4) and C_(0), C₂.

Methods: We checked the absorption profile of microemulsion cyclosporine group (N=15, ME group) and non-microeulsion cyclosporine group (N=15, NE group). All Patients had received renal transplantation at least 12 months before. Blood sampling for cyclosporine level was drawn before and at 1, 2, 3 hour after the cyclosporine morning dose (respectively C_(0), C₁, C₂ and C₃). AUC_(0-4) was calculated with the formula:256+C₁+0.9xC₂+1.4xC₃. Age, sex, body weight, serum creatinine and cyclosporine dose were not different between ME group and NE group, but duration after transplantation was significantly higher in NE group (4.7±0.8 versus 3.0±1.9 year, p<0.05).

Results: AUC_(0-4) in ME group was significantly higher than NE group (2,816±721 versus 2,055±658 ng.h/mL, p<0.05). AUC_(0-4)/dose, Cmax and Cmax/ dose were significantly higher in ME group. But these statistical differences were not consistent in both sexes. The difference of absorption profile between ME and NE group existed only in the female sex. In ME group, C₁ correlated best with AUC_(0-4) (C_(0):r=0.493, C₁:r=0.911, C₂:r=0.906, C₃:r= 0.789) and in NE group, C₂ was the best (C_(0):r= 0.064, C₁:r=0.958, C₂:r=0.980, C₃:r=0.912).

Conclusion: Microemulsion cyclosporine is more bioavailable than non-microemulsion cyclosporine in stable renal transplant patients. C₂ is better single time point marker for therapeutic drug monitoring in stable renal transplant patients than C_(0).