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Evolution to twice daily bolus intravenous tacrolimus: Optimizing efficacy and safety of calcineurin inhibitor delivery early post lung transplant

Gregory I. Snell, Steven Ivulich, Lauren Mitchell, Glen P. Westall, Bronwyn J. Levvey

Ann Transplant 2013; 18:399-407

DOI: 10.12659/AOT.883993

Published: 2013-08-07


Background: Achieving therapeutic levels of cyclosporine (CSA) or Tacrolimus (TAC) early post lung transplantation (LTx) is challenging. Gut dysmotility, renal dysfunction and seizure risk are variably present and problematic. This study reports a single center.
Material and Methods: All adult LTx recipients from Aug 06–Aug 11 were divided into 4 cohorts: A) intravenous (IV) CSA twice daily (BD) 6 hr bolus then oral CSA, n=63; B) sub-lingual (SL) TAC BD then oral TAC, n=90; C) oral TAC BD, n=18; and D) IV TAC BD 4hr bolus then oral TAC, n=62. CSA/TAC trough levels were measured at days 1–7, 14 and 28 aiming for target trough levels >250 ng/ml and >8ng/ml respectively.
Results: There were no differences in demographics, ICU and total length of stay between groups. Target trough levels were achieved in 13%*#, 26%*, 17% and 37%# of patients for Groups A-D respectively, (*#p<0.05) by day 7, increasing to 65%, 74%, 88% and 72% by day 14 (p=ns). Acute rejection at day 14 was seen in 3%*, 6%, 17%* and 5% respectively (*p<0.05) Acute rejection <90days was noted in 15%, 17%, 22% and 11% respectively (p=ns). No significant difference in neurotoxicity or acute nephrotoxicity was apparent across the groups.
Conclusions: Early post LTx, SL and oral routes of immunosuppressive administration are less efficacious than intravenous. BD bolus IV TAC achieved significantly higher target levels earlier, with correspondingly lower acute rejection rates and acceptable safety of administration.

Keywords: Lung Transplantation, acute rejection, Tacrolimus



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