Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration

Julia E M van Dommelen; Heleen Grootjans; Esther V Uijtendaal; Dieuwertje Ruigrok; Bart Luijk; Matthijs van Luin; Wouter Bult; Dylan W de Lange; Nuray Kusadasi; Joep M Droogh; Toine C G Egberts; Erik A M Verschuuren; Maaike A Sikma

doi:10.1007/s40262-024-01368-1

Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration

Clin Pharmacokinet. 2024 Apr 6. doi: 10.1007/s40262-024-01368-1. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Pharmacy, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
² Department of Internal Medicine, Section Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
³ Department of Pulmonology, Tuberculosis and Lung Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Pulmonary Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵ Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Intensive Care and Dutch Poisons Information Center, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
⁷ Department of Intensive Care, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
⁸ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁹ Department of Intensive Care and Dutch Poisons Information Center, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands. M.A.Sikma@umcutrecht.nl.

^# Contributed equally.

PMID: 38581638
DOI: 10.1007/s40262-024-01368-1

Abstract

Background and objective: High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx.

Methods: Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission.

Results: We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9-14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI - 11.3 to - 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8-1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0-2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar.

Conclusions: Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.