期刊
ANNALS OF TRANSPLANTATION
卷 26, 期 -, 页码 -出版社
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/AOT.928817
关键词
Drug Antagonism; Drug Interactions; Drug Synergism; Kidney Transplantation; Tacrolimus
This study found that the combination of EVL and TAC has a synergistic effect on the proliferation of mitogen-activated PBMCs within the therapeutic concentration range used in renal transplantation. However, at concentrations higher than those clinically used, these drugs antagonize each other.
Background: Everolimus (EVL) plus tacrolimus (TAC) therapy is effective and safe in renal transplantation. However, the pharmacokinetic and pharmacodynamic information for EVL combined with TAC is limited. We investigated the pharmacodynamic drug-drug interaction between EVL and TAC at their therapeutic concentration range. Material/Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 22 healthy participants aged 22 to 24 years were cultured with concanavalin A (Con A) in the presence of EVL and/or TAC for 4 days, and the proliferation rate of the PBMCs was calculated. Results: TAC promoted the inhibitory efficacy of EVL against the mitogen-activated proliferation of PBMCs at the EVL therapeutic concentration range. When 0.175 ng/ml or more of TAC was combined with 30 ng/mL or more of EVL, the antagonistic effect of TAC on the inhibitory efficacy of EVL against the mitogen-activated proliferation of PBMCs was observed. Conversely, when 0.4 ng/mL TAC and 10 ng/mL or more of EVL were combined, the antagonistic effect of EVL on the inhibitory efficacy of TAC against the mitogen-activated proliferation of PBMCs was observed. Conclusions: The pharmacodynamic synergistic efficacy of EVL and TAC in combination on mitogen-activated PBMCs was evident at the therapeutic concentration range, which is used in renal transplantation. However, these drugs antagonize each other to suppress the proliferation of activated PBMCs at concentrations higher than those clinically used.
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