Correlation between pharmacokinetics of tacrolimus and pharmacodynamics on NFAT-regulated gene expression in stable kidney transplant recipients 
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Correlation between pharmacokinetics of tacrolimus and pharmacodynamics on NFAT-regulated gene expression in stable kidney transplant recipients
. Clin Nephrol. 2016 Dec 27;: Authors: Keller F, Sommerer C, Giese T, Zeier M, Schröppel B Abstract Gene expression regulated by the transcription factor NFAT (nuclear factor of activated T-cells) has been proposed for monitoring the pharmacodynamic effect of calcineurin inhibitors. We aimed to correlate the pharmacokinetics of tacrolimus with the suppression of NFAT-regulated gene expression. Tacrolimus trough (Ctrough) and peak concentrations (Cpeak) were measured by LC-MS. The effect on NFAT-regulated gene expression at trough (Etrough) and at peak levels (Epeak) were determined by qRT-PCR. The pharmacodynamic concentration producing the half-maximum effect (CE50) and the Hill coefficient (H) were estimated from Etrough and from Epeak. Ten stable kidney transplant recipients on triple immunosuppression with prednisolone, mycophenolate, and tacrolimus were analyzed. Median age was 58 years, median time since transplant was 84 months, and median serum creatinine was 249 µmol/L. The immunosuppressive effect on NFAT-regulated genes at trough concentrations was 38% (Etrough), and the effect at peak concentrations was 59% (Epeak) of maximum immunosuppression (Emax). The pharmacodynamic parameters of the action of tacrolimus were estimated with the Hill coefficient H at 1.5 and the CE50 a...
Source: Clinical Nephrology - Category: Urology & Nephrology Authors: Tags: Clin Nephrol Source Type: research