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Decreasing Tacrolimus Concentrations in Routine Therapeutic Drug Monitoring Data Indicate Adherence to Updated Therapeutic Goals

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Resumo:Background: Tacrolimus is a key immunosuppressive drug used to prevent organ rejection after transplantation. Its narrow therapeutic window and high interindividual pharmacokinetic variability make therapeutic drug monitoring (TDM) essential. This study aimed to (1) characterize long-term trends in tacrolimus concentrations; (2) assess potential seasonal variation; and (3) evaluate the suitability of patient medians as a tool for laboratory quality monitoring. Methods: A retrospective analysis was conducted on 113,735 tacrolimus whole-blood results obtained between 2006 and 2024 at Uppsala University Hospital, Sweden. Samples were analyzed using immunoassays on the Hitachi 912 (Microgenics) until 2008, the Abbott Architect until 2021, and the Roche Cobas Pro e 801 thereafter. Annual patient medians and percentiles (10th, 25th, 50th, 75th, and 90th) were calculated. Seasonal variation was assessed by comparing monthly test volumes and concentration distributions. Results: The annual number of tacrolimus results increased from 5616 in 2006 to 7320 in 2024, comprising 67,133 male and 46,602 female patient results. All distribution metrics declined steadily over the study period, with median tacrolimus concentrations decreasing by 20–30%. The July test volume was approximately 15% lower than in other months, but no meaningful seasonal variation in tacrolimus concentrations was observed; monthly medians and percentiles remained stable throughout the year. Conclusions: Tacrolimus concentrations at the population level have decreased consistently over nearly two decades. These findings likely reflect evolving clinical practice, including dose minimization strategies to reduce toxicity. Patient medians proved robust over time and may serve as a useful adjunct to conventional quality control, particularly when commercial control materials do not fully mimic patient sample behavior.
Autores principais:Larsson, Anders
Outros Autores:Saldeen, Johan; Cedernaes, Jonathan; Eriksson, Mats B.; Karlsson, Mathias; Hamberg, Anna Karin
Assunto:immunosuppressive patient median tacrolimus therapeutic drug monitoring transplantation Medicine (miscellaneous) General Biochemistry,Genetics and Molecular Biology
Ano:2026
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL
Descrição
Resumo:Background: Tacrolimus is a key immunosuppressive drug used to prevent organ rejection after transplantation. Its narrow therapeutic window and high interindividual pharmacokinetic variability make therapeutic drug monitoring (TDM) essential. This study aimed to (1) characterize long-term trends in tacrolimus concentrations; (2) assess potential seasonal variation; and (3) evaluate the suitability of patient medians as a tool for laboratory quality monitoring. Methods: A retrospective analysis was conducted on 113,735 tacrolimus whole-blood results obtained between 2006 and 2024 at Uppsala University Hospital, Sweden. Samples were analyzed using immunoassays on the Hitachi 912 (Microgenics) until 2008, the Abbott Architect until 2021, and the Roche Cobas Pro e 801 thereafter. Annual patient medians and percentiles (10th, 25th, 50th, 75th, and 90th) were calculated. Seasonal variation was assessed by comparing monthly test volumes and concentration distributions. Results: The annual number of tacrolimus results increased from 5616 in 2006 to 7320 in 2024, comprising 67,133 male and 46,602 female patient results. All distribution metrics declined steadily over the study period, with median tacrolimus concentrations decreasing by 20–30%. The July test volume was approximately 15% lower than in other months, but no meaningful seasonal variation in tacrolimus concentrations was observed; monthly medians and percentiles remained stable throughout the year. Conclusions: Tacrolimus concentrations at the population level have decreased consistently over nearly two decades. These findings likely reflect evolving clinical practice, including dose minimization strategies to reduce toxicity. Patient medians proved robust over time and may serve as a useful adjunct to conventional quality control, particularly when commercial control materials do not fully mimic patient sample behavior.