期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 2, 期 2, 页码 173-178出版社
BLACKWELL MUNKSGAARD
DOI: 10.1034/j.1600-6143.2002.020209.x
关键词
calcineurin; pharmacodynamic; renal transplantation; tacrolimus
The toxicity of tacrolimus (FK) despite therapeutic levels (trough) has led us to investigate its relationship with the inhibition of calcineurin (CaN) in recently transplanted renal patients. Twenty-one patients taking FK had blood drawn on day 3 and 14 at 0,1,2,3,4 and 6h. CaN activity was measured by its ability to cleave P-32 from a previously radiolabeled phosphorylated 19-amino acid peptide. Radioactivity was quantitated and results were converted to units CaN. FK concentration was measured simultaneously. Maximal suppression of CaN occurred after 2 h on both days. Unlike FK levels, CaN activity returned to predose levels by 6 h. Comparing mean CaN activity at time 0 with each subsequent time showed statistical significance at hours 1, 2 and 3 on each day. Comparing mean FK concentrations, similarly, revealed statistical significance at all hours. Area under CaN activity curve (AU(CaN)) vs. mean FK levels failed to show significance. However, comparing AUC(CaN) with mean CaN activity was significant throughout. CaN capacity at time 0 and 6 h (day 14) resulted in the best estimate of CaN inhibition. Prior to steady-state (day 3), the best estimate occurred at 2h. No single FK concentration seemed to be a reliable indicator of CaN inhibition.
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