Correlation between the pharmacological efficacy of cyclosporine and tacrolimus as evaluated by the lymphocyte immunosuppressant sensitivity test (LIST) and the MTT assay procedure in patients before and after renal transplantation.
OBJECTIVE
Cyclosporine and tacrolimus are calcineurin inhibitors that are used to prevent acute rejection in renal transplant recipients. The lymphocyte immunosuppressant sensitivity test (LIST) can predict the pharmacological efficacy of these immunosuppressive agents for renal transplant recipients. There is a correlation between cyclosporine and tacrolimus pharmacological efficacy as evaluated by LIST by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay procedure prior to renal transplantation. However, the LIST can also evaluate patients before and after the transplantation.


METHODS
The present study examined the relationship between cyclosporine and tacrolimus pharmacological efficacy by LIST using the MTT assay in 16 renal transplant recipients at 1, 3 and 12 months after transplantation, as well as before the operation.


RESULTS
The relationship of cyclosporine and tacrolimus pharmacological efficacy gave a significant Kendall and Spearman's coefficient correlation in these transplant recipients by the LIST using the MTT assay procedure immediately prior to renal transplantation (rk = 0.711, rs = 0.877, p < 0.01). Furthermore, correlations between the cyclosporine and tacrolimus IC50 values were also observed with a significant Kendall and Spearman's coefficient correlation at 1 and 12 months after transplantation (rk1month = 0.65, rs1month = 0.829, p < 0.01, and k12month = 0.433, rs12month = 0.603, p < 0.01, respectively). However, no statistically significant relationship was observed between the pharmacological efficacies of the calcineurin inhibitors at 3 months after transplantation (rk3month = 0.117, rs3month = 0.1, p > 0.05).


CONCLUSIONS
Both cyclosporine and tacrolimus exhibit pharmacological efficacy by the inhibition of calcineurin. However, the correlation between cyclosporine and tacrolimus pharmacological efficacies may be altered, due to immunosuppressive therapy or clinical events at 3 months after renal transplantation.
Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan. sugiyama-nii@umin.ac.jp
K
K
Sugiyama
K
K
Isogai
A
A
Toyama
H
H
Satoh
K
K
Saito
Y
Y
Nakagawa
M
M
Tasaki
K
K
Takahashi
T
T
Hirano
D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D007166:Immunosuppressive Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016572:Cyclosporine; C022616:thiazolyl blue; D016559:Tacrolimus