Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets

Benjamin Philosophe, Nicolae Leca, Patricia M West-Thielke, Timothy Horwedel, Christine Culkin-Gemmell, Kristin Kistler, Daniel R Stevens, Benjamin Philosophe, Nicolae Leca, Patricia M West-Thielke, Timothy Horwedel, Christine Culkin-Gemmell, Kristin Kistler, Daniel R Stevens

Abstract

The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation.

Keywords: calcineurin inhibitor; daily; monitoring; pharmacokinetics and drug metabolism; renal disease; tacrolimus; transplantation (TRP).

© 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Figures

Figure 1
Figure 1
AUC correlations and associated trough concentrations 21, 24, and 27 hours postdose. AUC0–24, area under the concentration–time curve over 24 hours; C21, C24, C27, concentration at 21, 24, and at 27 hours, respectively.

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