Validation of an LC–MS/MS Method to Measure Tacrolimus in Rat Kidney and Liver Tissue and Its Application to Human Kidney Biopsies

Noll, Benjamin; Coller, Janet K.; Somogyi, Andrew A.; Morris, Raymond G.; Russ, Graeme; Hesselink, Dennis A.; Gelder, Teun van; Sallustio, Benedetta C.

doi:10.1097/ftd.0b013e31828e8162

Cited by 31 publications

(27 citation statements)

References 30 publications

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“…In contrast, a poor correlation has been reported between Banff scores and the blood level of TAC (r 2 = 0.0281) [123]. In kidney transplant recipients (two patients) [144], a decrease in TAC was observed in tissue and C 0 whole blood over time (16–300 days) but, there was no correlation between the two measurements.…”

Section: Intratissue Concentrationmentioning

confidence: 99%

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Ghareeb

Akhlaghi

2015

Bioanalysis

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Immunosuppressive drugs used in solid organ transplants typically have narrow therapeutic windows and high intra- and intersubject variability. To ensure satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in any successful posttransplant maintenance therapy. Currently, recommendations for optimum immunosuppressant concentrations are based on blood/plasma measurements. However, they introduce many disadvantages, including poor prediction of allograft survival and toxicity, a weak correlation with drug concentrations at the site of action and the invasive nature of the sample collection. Thus, alternative matrices have been investigated. This paper reviews tandem-mass spectrometry (LC–MS/MS) methods used for the quantification of immunosuppressant drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood and intracellular and intratissue sampling. The advantages, disadvantages and clinical application of such alternative mediums are discussed. Additionally, sample extraction techniques and basic chromatography information regarding these methods are presented in tabulated form.

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Section: Intratissue Concentrationmentioning

confidence: 99%

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Ghareeb

Akhlaghi

2015

Bioanalysis

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“…Several assays have been developed for the quantification of the drug in biological samples. The most common methods for routine FK506 monitoring are monoclonal antibody-based immunoassays, while liquid chromatography-tandem mass spectrometry (LC-MS) is currently considered as the reference method [4][5][6][7]. LC-MS provides the most specific routine drug measurement, whereas immunoassays show a notable crossreactivity with inactive metabolites [4,8], especially MIII and MV [9].…”

Section: Introductionmentioning

confidence: 99%

Label-free quantification of Tacrolimus in biological samples by atomic force microscopy

Menotta

Biagiotti

Streppa

et al. 2015

Analytica Chimica Acta

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“…CNI-induced nephrotoxicity is likely to be related to intra-renal concentrations of CNIs which may not be properly reflected by whole-blood CNI concentrations. [57][58][59][60] CYP3A5 is the only CYP3A isozyme expressed in the kidney and may limit local exposure to CNIs by intra-renal metabolism. [61,62] Zheng et al [63] demonstrated that Tac concentrations in the renal epithelium of CYP3A5 expressers are 53% lower compared with CYP3A5 non-expressers.…”

Section: Nephrotoxicitymentioning

confidence: 99%

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Tang

Andrews

Gelder

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

120

114

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Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a~40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.ARTICLE HISTORY

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Validation of an LC–MS/MS Method to Measure Tacrolimus in Rat Kidney and Liver Tissue and Its Application to Human Kidney Biopsies

Abstract: The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

Cited by 31 publications

References 30 publications

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Label-free quantification of Tacrolimus in biological samples by atomic force microscopy

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

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