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Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration
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Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration
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Journal Article
Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration
2024
Overview
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.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
Acute Kidney Injury - epidemiology
/ Acute Kidney Injury - etiology
/ Adult
/ Enzymes
/ Female
/ Graft Rejection - epidemiology
/ Graft Rejection - prevention & control
/ Humans
/ Immunosuppressive Agents - administration & dosage
/ Immunosuppressive Agents - blood
/ Immunosuppressive Agents - pharmacokinetics
/ Intensive Care Units - statistics & numerical data
/ Kidneys
/ Length of Stay - statistics & numerical data
/ Lung Transplantation - adverse effects
/ Male
/ Medicine
/ Original
/ Patients
/ Tacrolimus - administration & dosage
/ Tacrolimus - pharmacokinetics
/ Toxicity
