Abstract: SA-PO642

Antibiotics: A Novel Factor Associated with Tacrolimus Trough Variability in Kidney Transplantation

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Lee, John Richard, Weill Cornell Medicine-, New York, New York, United States
  • Zheng, Yuanpu, New York Presbyterian Hospital, New York, New York, United States
  • Wagner, Michael P., New York Presbyterian Hospital, New York, New York, United States
  • Dadhania, Darshana, Weill Cornell Medicine-, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine-, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine-, New York, New York, United States
Background

We previously reported a relationship of the gut microbiota to tacrolimus dosing requirements. Based upon this data, we hypothesize that antibiotics, which are known to alter the gut microbiota, is associated with tacrolimus trough variability.

Methods

We performed a retrospective chart review of subjects who received a kidney transplantation at our institution from 2012 to 2013. We divided the population into subjects who received antibiotics during the first month of transplantation (Abx Group, N=60) and subjects who did not (No Abx Group, N=169) (Fig A). We evaluated whether antibiotics increase tacrolimus trough levels and tacrolimus trough level over dosing (C/D) in the Abx Group and whether antibiotics increase tacrolimus trough variability as measured by standard deviation (SD) and coefficient of variation (CV) between post op days 31 to 45.

Results

In the Abx Group, 48 subjects had a tacrolimus trough level measured prior to antibiotic administration and these subjects had increased tacrolimus trough levels and increased tacrolimus C/D, 7 and 15 days after antibiotic administration (Fig 2B, 2C). Subgroup analysis of type of antibiotics suggested increasing C/D after 7 days after antibiotic administration in penicillin type antibiotics and cephalosporin type antibiotics (P=0.08, 0.09, respectively). Tacrolimus trough variability as measured by SD and CV between post op days 31 to 45 was significantly different between the Abx Group and the No Abx Group (SD median 2.6 vs 1.6, P=0.03; CV median 0.29 vs. 0.18, P=0.02, Wilcoxon rank sum test) (Fig 3).

Conclusion

Our identification of antibiotics' association with tacrolimus trough variability highlights the need to measure tacrolimus trough levels after antibiotic administration.

Funding

  • Other NIH Support