Tacrolimus Trough Concentrations Increase in Intestinal Transplant Recipients During Episodes of Acute Cellular Rejection
1Department of Pharmacy and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA
2Department of Pharmacy, Memorial University Medical Center, Savannah, GA
3Northern Institute for Cancer Research at Newcastle University, Tyne and Wear, United Kingdom
4Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
5Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, Cleveland, OH
6Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
7Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Meeting: 2015 American Transplant Congress
Abstract number: A277
Keywords: Adverse effects, FK506, Intestinal transplantation, Rejection
Session Information
Session Name: Poster Session A: Small Bowel All Topics
Session Type: Poster Session
Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Introduction: Acute cellular rejection (ACR) in small bowel transplant recipients is expected to increase intestinal permeability and to reduce intestinal CYP3A/p-glycoprotein activity. These changes may increase blood concentrations of tacrolimus and result in acute toxicity. We evaluated the impact of ACR episodes on dose-normalized tacrolimus blood concentrations in intestinal transplant recipients.
Methods: Adult intestinal transplant recipients who had ACR from 02/1998 to 07/2013 at a single center were reviewed. Patient history, ACR information, laboratory values, and drug dosing were collected. Changes in dose-normalized tacrolimus levels were assessed starting 30 days before, during, and up to 30 days after documented ACR resolution. Secondary outcomes included evaluating impact of ACR grade, ACR treatment, time post-transplantation, and initial or recurrent episode.
Results: 285 ACR episodes in 113 intestinal transplant recipients were included in the analysis. Median dose-normalized concentrations were different before, during, and after ACR (1.7ng/mL/mg vs. 4.0ng/mL/mg vs. 2.2ng/mL/mg, p=0.014). Median percent change in dose-normalized tacrolimus was significantly different across ACR severity (p=0.014), time post-transplant (p=0.007), and initial versus recurrent ACR (p=0.013). SCr was significantly higher during ACR (1.3mg/dL vs. 1.5mg/dL vs. 1.2mg/dL, p=0.001). Dose-normalized tacrolimus concentrations were elevated during ACR and this was associated with the increase in SCr.
Conclusion: There is potential for increased systemic exposure and toxicity of tacrolimus and other orally administered drugs in small bowel transplant patients during ACR. Further pharmacokinetic investigation is warranted.
To cite this abstract in AMA style:
Lichvar A, Deen D, Johnson H, Bonner J, Bond G, Costa G, Cruz R, Abu-Elmagd K, Venkataramanan R. Tacrolimus Trough Concentrations Increase in Intestinal Transplant Recipients During Episodes of Acute Cellular Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/tacrolimus-trough-concentrations-increase-in-intestinal-transplant-recipients-during-episodes-of-acute-cellular-rejection/. Accessed June 1, 2025.« Back to 2015 American Transplant Congress