Intrapatient variability in tacrolimus trough levels after solid organ transplantation varies at different postoperative time periods Article Swipe
Itai Gueta
,
Noa Markovits
,
Havatzelet Yarden‐Bilavsky
,
Eugenia Raichlin
,
Dov Freimark
,
Jacob Lavee
,
Ronen Loebstein
,
Yael Peled
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1111/ajt.15134
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1111/ajt.15134
To the Editor: We thank Lemaitre et al1Lemaitre F, Tron C, Jezequel C, Verdier CM, Rayer M. Intra-patient variability in solid-organ transplantation: should we make the first move earlier [published online ahead of print 2018]? Am J Transplant. https://doi.org/10.1111/ajt.15107Google Scholar for their letter regarding our manuscript describing the association between intrapatient variability (IPV) of tacrolimus (TAC) trough levels and long-term outcomes in heart transplant (HTx) patients. Indeed, in our study2Gueta I Markovits N Yarden-Bilavsky H et al.High tacrolimus trough level variability is associated with rejections after heart transplant.Am J Transplant. 2018; 18: 611Abstract Full Text Full Text PDF Scopus (43) Google Scholar we found that high TAC through level variability at 3-12 months post-HTx was associated with higher rates of graft rejection at odds ratio (OR) of 8.52. However, we wish to clarify that due to the wide 95% confidence interval (1.63-44.53), the minimum odds might also be 1.63 and hence prefer not to define the risk of high TAC through level variability as "tremendous."1Lemaitre F, Tron C, Jezequel C, Verdier CM, Rayer M. Intra-patient variability in solid-organ transplantation: should we make the first move earlier [published online ahead of print 2018]? Am J Transplant. https://doi.org/10.1111/ajt.15107Google Scholar Given the TAC half-life (12 hours for immediate release formula), we absolutely agree with the authors that IPV can be estimated much earlier than 6, and even 3 months post-HTx. However, we believe that investigators should distinguish IPV (and its associated outcomes) during the early (first 3 months) from the late postoperative period. Within the former, the first 1 to 2 weeks should also be separately examined as they are characterized by acute physiological changes in intestinal p-glycoprotein and CYP3A4 expression that are secondary to the major operation itself. Additionally, varying drug regimens (other than TAC) expose recipients to drug-drug interactions, enzyme induction, and inhibition.3Sikma MA van Maarseveen EM van de Graaf EA et al.Pharmacokinetics and toxicity of tacrolimus early after heart and lung transplantation.Am J Transplant. 2015; 15: 2301-2313Crossref PubMed Scopus (97) Google Scholar Taken together, these changes may influence TAC pharmacokinetics on a daily basis and hence the IPV. From the point of view of pharmacodynamics, concomitant immunosuppressive agents introduced peri-operatively (eg, antithymocyte globulin and high dose corticosteroids) may also confound TAC related outcomes per se. Hence, the IPV and its associated outcomes might differ between the early postoperative period and the late one. To conclude, although we agree that patients with high TAC through level variability should be identified early during the postoperative period, we believe that future studies should analyze the IPV and outcomes over several time periods as deemed appropriate. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
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Metadata
- Type
- letter
- Language
- en
- Landing Page
- https://doi.org/10.1111/ajt.15134
- http://www.amjtransplant.org/article/S1600613522089705/pdf
- OA Status
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- Cited By
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- References
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- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W2894617003Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1111/ajt.15134Digital Object Identifier
- Title
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Intrapatient variability in tacrolimus trough levels after solid organ transplantation varies at different postoperative time periodsWork title
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letterOpenAlex work type
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-10-05Full publication date if available
- Authors
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Itai Gueta, Noa Markovits, Havatzelet Yarden‐Bilavsky, Eugenia Raichlin, Dov Freimark, Jacob Lavee, Ronen Loebstein, Yael PeledList of authors in order
- Landing page
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https://doi.org/10.1111/ajt.15134Publisher landing page
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https://www.amjtransplant.org/article/S1600613522089705/pdfDirect link to full text PDF
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://www.amjtransplant.org/article/S1600613522089705/pdfDirect OA link when available
- Concepts
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Medicine, Tacrolimus, Odds ratio, Confidence interval, Organ transplantation, Heart transplantation, Trough (economics), Transplantation, Internal medicine, Cardiology, Surgery, Macroeconomics, EconomicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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12Total citation count in OpenAlex
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2024: 1, 2022: 3, 2021: 4, 2020: 3, 2019: 1Per-year citation counts (last 5 years)
- References (count)
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3Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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