Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy
Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentration...
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2021-09-01
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| Online Access: | https://www.mdpi.com/1999-4923/13/10/1576 |
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| author | Magdalena Bodnar-Broniarczyk Magdalena Durlik Teresa Bączkowska Katarzyna Czerwińska Ryszard Marszałek Tomasz Pawiński |
| author_facet | Magdalena Bodnar-Broniarczyk Magdalena Durlik Teresa Bączkowska Katarzyna Czerwińska Ryszard Marszałek Tomasz Pawiński |
| author_sort | Magdalena Bodnar-Broniarczyk |
| collection | DOAJ |
| description | Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with <i>tert</i>-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C<sub>0</sub>) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac<sup>13</sup>C,D<sub>2</sub> as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg. |
| first_indexed | 2024-03-10T06:16:20Z |
| format | Article |
| id | doaj.art-8085468a116040dabed66bdf13854e14 |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:16:20Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8085468a116040dabed66bdf13854e142023-11-22T19:37:50ZengMDPI AGPharmaceutics1999-49232021-09-011310157610.3390/pharmaceutics13101576Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive TherapyMagdalena Bodnar-Broniarczyk0Magdalena Durlik1Teresa Bączkowska2Katarzyna Czerwińska3Ryszard Marszałek4Tomasz Pawiński5Department of Drug Chemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Drug Bioanalysis and Analysis, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, PolandDepartment of Drug Chemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, PolandTacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with <i>tert</i>-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C<sub>0</sub>) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac<sup>13</sup>C,D<sub>2</sub> as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg.https://www.mdpi.com/1999-4923/13/10/1576tacrolimuskidney and liver transplantationtissue concentrationLC-MS/MSTDM |
| spellingShingle | Magdalena Bodnar-Broniarczyk Magdalena Durlik Teresa Bączkowska Katarzyna Czerwińska Ryszard Marszałek Tomasz Pawiński Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy Pharmaceutics tacrolimus kidney and liver transplantation tissue concentration LC-MS/MS TDM |
| title | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
| title_full | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
| title_fullStr | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
| title_full_unstemmed | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
| title_short | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
| title_sort | kidney and liver tissue tacrolimus concentrations in adult transplant recipients the influence of the whole blood and tissue concentrations on efficiency of treatment during immunosuppressive therapy |
| topic | tacrolimus kidney and liver transplantation tissue concentration LC-MS/MS TDM |
| url | https://www.mdpi.com/1999-4923/13/10/1576 |
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