13th Congress of the Polish Transplantation Society: Part IIExperimental transplantationEvaluation of the Relationship Between Concentrations of Tacrolimus Metabolites, 13-O-Demethyl Tacrolimus and 15-O-Demethyl Tacrolimus, and Clinical and Biochemical Parameters in Kidney Transplant Recipients
Section snippets
Materials and Methods
Blood samples were obtained from patients who gave their written informed consent to participate in the study. Sixty-three stable patients who underwent kidney transplantation were included in the study. Their median age was 51.3 (range, 22–73) years. The study group included 36 male and 27 female subjects. The median posttransplant time was 36.1 (range, 1–209) months. Trough blood samples of 2 mL were collected during routine outpatient visits into ethylene-diamine tetraacetic acid
Results
Patients' demographics and concentrations of Tac and its metabolites are shown in Table 1. None of the patients had detectable 31-DMT blood levels. There was a positive correlation between 13-DMT/Tac and ALAT (r = 0.29, P = .046) (Fig 1) and a similar relationship between 13-DMT and ALAT (r = 0.41, P = .004). We also found a negative correlation between 13-DMT/Tac and hemoglobin (r = −0.33, P = .008) (Fig 1). A similar relationship was observed between Tac dose per kilogram body weight and
Discussion
In this study we have evaluated the concentrations of Tac and its main metabolites using LC/MS/MS in kidney transplant recipients. There have been some previous reports on quantification of Tac metabolites using the same method [5], [9], [10], but data on the clinical importance of these metabolites are limited.
We observed a positive correlation between 13-DMT/Tac and ALAT. This could be explained by the fact that liver dysfunction leads to accumulation of Tac and its metabolites. Over 95% of
Conclusion
Our data show that 13-DMT/Tac ratio is significantly associated with liver function and complete blood count parameters. The clinical significance of these findings is unclear, but may reflect changes in the metabolism of the drug under special conditions, 13-DMT accumulation during liver dysfunction, and higher Tac clearance in the case of anemia. However, the findings could also suggest that the 13-DMT/Tac ratio is a marker of myelotoxicity and hepatotoxicity. In this case, quantification of
Acknowledgments
The authors thank Astellas Pharma for kindly donating standards of tacrolimus metabolites.
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A simple and easy-to-perform liquid chromatography–mass spectrometry method for the quantification of tacrolimus and its metabolites in human whole blood. Application to the determination of metabolic ratios in kidney transplant patients
2021, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :The gold standard method for the quantification of tacrolimus in blood is liquid chromatography-tandem mass spectrometry (LC-MS/MS) [5]. However, few papers have described LC-MS/MS methods allowing for the simultaneous quantification of tacrolimus and its three main metabolites [6–8]. We aimed to develop and validate a simple, sensitive, and robust LC–MS/MS method for the simultaneous quantification of tacrolimus and its three desmethylated metabolites, M−I, M−II and M−III, and to describe the blood pharmacokinetic profile of tacrolimus and its metabolites in a cohort of kidney transplant patients.
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This study was supported by grants from the Polish National Center of Research and Development (NR13014410) and the Polish National Science Centre (2013/09/B/NZ2/00275).