Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.

Autor: Du W; Department of Pharmacy, China-Japan Friendship Hospital, Chaoyang District, Beijing, China., Wang X; Department of Pharmacy, China-Japan Friendship Hospital, Chaoyang District, Beijing, China., Zhang D; Department of Pharmacy, China-Japan Friendship Hospital, Chaoyang District, Beijing, China., Zuo X; Department of Pharmacy, China-Japan Friendship Hospital, Chaoyang District, Beijing, China. subpharm@163.com.; Department of Dermatology, China-Japan Friendship Hospital, Chaoyang District, Beijing, China. subpharm@163.com.
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2024 May; Vol. 80 (5), pp. 747-757. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1007/s00228-024-03640-6
Abstrakt: Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation.
Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C 0 ) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C 0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C 0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality.
Results: The influence of CYP3A5*3 polymorphism was only significant for C 0 and IPV during the first 3 months. Low C 0 (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C 0 /High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C 0 or IPV alone.
Conclusion: A combination of Low C 0 /High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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