BACKGROUND. The gut microbiome impacts drug absorption, metabolism, and distribution and was recently shown to be associated with tacrolimus dosing requirements. Since antibiotics can alter the gut microbiota, we investigated the hypothesis that antibiotics increase intra-patient variability in tacrolimus trough concentrations, an identified risk factor for kidney graft failure.

METHODS. We conducted a retrospective review of electronic medical records of 271 kidney transplant recipients who received their kidney transplants from January 2012 to June 2013 at our center. We collected data recording antibiotic therapy and tacrolimus trough concentrations. We divided the study cohort into 2 groups: subjects who received antibiotics during the first month of transplantation (Early Abx Group) and subjects who did not (No Early Abx Group) and evaluated whether the Early Abx Group had increased intra-patient variability in tacrolimus trough levels, as measured by standard deviation (SD) and coefficient of variation (CV), in the 3 weeks following post-transplant month 1.

RESULTS. Seventy (26%) of the 271 subjects received antibiotics during the first month of transplantation (Early Abx Group), and 201 (74%) did not (No Early Abx Group). During the three weeks following post-transplant month 1, the Early Abx Group had significantly more intra-patient variability in tacrolimus trough concentrations than the No Early Abx Group: SD: 2.5±1.3 mg/dL vs. 2.1±1.7 mg/dL, P=0.01, Wilcoxon rank sum test, respectively (Fig. 1A); CV: 28%±16% vs. 23±17%, P=0.01, Wilcoxon rank sum test, respectively (Fig. 1B). The mean±SD tacrolimus trough concentrations, however, were not significantly different between the two groups during the same time frame (8.8 ±1.6 vs. 8.9±1.8 mg/dL, P=0.68, Wilcoxon rank sum test) (Fig. 1C).

CONCLUSIONS. Our original finding that antibiotics increase inter-patient variability in tacrolimus trough concentrations highlights the need for close monitoring of tacrolimus trough concentrations after antibiotic administration.

CITATION INFORMATION: Zheng Y, Lee J, Masand A, Dadhania D, Thangamani M, Suthanthiran M. Tacrolimus Precision Medicine: Antibiotics Increase Intra-Patient Variability in Tacrolimus Trough Concentrations in Kidney Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

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