Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Full metadata record
DC FieldValueLanguage
dc.contributor.authorNoll, B.-
dc.contributor.authorColler, J.-
dc.contributor.authorSomogyi, A.-
dc.contributor.authorMorris, R.-
dc.contributor.authorRuss, G.-
dc.contributor.authorHesselink, D.-
dc.contributor.authorvan Gelder, T.-
dc.contributor.authorSallustio, B.-
dc.identifier.citationTherapeutic Drug Monitoring, 2011; 33(6):688-693-
dc.description.abstractTherapeutic drug monitoring is used to individualize cyclosporine A (CsA) dosing after transplantation. However, immunosuppressant concentrations within the graft may better predict clinical outcomes, including toxicity. This study aimed to develop a method suitable for CsA measurement using routine fine-needle biopsy samples. CsA was quantified retrospectively in kidney and liver tissues from 10 rats administered CsA, and 21 core needle kidney biopsies taken from renal transplant patients with suspected graft dysfunction. Dried biopsies were weighed (mean ± SD weights of 0.22 ± 0.18 mg), enzymatically solubilized, and then CsA was extracted and quantified using online 2-dimensional liquid chromatography-tandem mass spectrometry. The method was linear (r² > 0.997, n = 10), accurate, and precise (quality control and calibrator coefficient of variation and bias <15%), with minimal matrix effects (coefficient of variation and bias <15%). Reproducibility of tissue weight measurements was confirmed by retrospective DNA quantitation, with a significant linear correlation between weight and total DNA concentration (r² = 0.988). In rats, there was a significant linear correlation between CsA concentrations in liver and kidney tissues (r² = 0.996) but there was no correlation between blood (C0) and tissue CsA concentrations (Spearman r = 0.430 and 0.503, P > 0.05). Similarly, in 16 transplant patients, for whom blood CsA concentrations (C2) were available within 1 day of the renal biopsy being performed, there was no significant correlation between CsA concentrations in blood and kidney tissue (Spearman r = 0.168, P > 0.05). In situ CsA measurements acquired using this method could make an easy transition into clinical use due to their retrospective nature and minimal disruption to current clinical protocols and could provide an additional tool for optimizing clinical outcomes in the future.-
dc.description.statementofresponsibilityBenjamin D. Noll, Janet K. Coller, Andrew A. Somogyi, Raymond G. Morris, Graeme R. Russ, Dennis A. Hesselink, Teun van Gelder, and Benedetta C. Sallustio-
dc.publisherLippincott Williams & Wilkins-
dc.rights© 2011 Lippincott Williams & Wilkins, Inc.-
dc.subjectCsA tissue measurements-
dc.subjecttherapeutic drug monitoring-
dc.titleMeasurement of Cyclosporine A in rat tissues and human kidney transplant biopsies - A method suitable for small (<1 mg) samples-
dc.typeJournal article-
dc.identifier.orcidColler, J. [0000-0002-8273-5048]-
dc.identifier.orcidSomogyi, A. [0000-0003-4779-0380]-
dc.identifier.orcidSallustio, B. [0000-0002-0186-3073]-
Appears in Collections:Aurora harvest 7
Pharmacology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.