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
| Autor: | Magdalena Bodnar-Broniarczyk, Katarzyna Czerwińska, Tomasz Pawinski, T Bączkowska, Ryszard Marszałek, Magdalena Durlik |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Kidney
medicine.medical_specialty business.industry kidney and liver transplantation Urology Pharmaceutical Science chemical and pharmacologic phenomena Article Tacrolimus RS1-441 TDM stomatognathic diseases Pharmacy and materia medica Therapeutic index medicine.anatomical_structure Pharmacokinetics Liquid chromatography–mass spectrometry Medicine Protein precipitation Centrifugation LC-MS/MS business tacrolimus tissue concentration Whole blood |
| Zdroj: | Pharmaceutics Volume 13 Issue 10 Pharmaceutics, Vol 13, Iss 1576, p 1576 (2021) |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13101576 |
| Popis: | 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 tert-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 (C0) 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 Tac13C,D2 as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg. |
| Databáze: | OpenAIRE |
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