Abstract:
BACKGROUND:Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. METHODS:Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). RESULTS:Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. CONCLUSIONS:The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Noll BD,Coller JK,Somogyi AA,Morris RG,Russ GR,Hesselink DA,Van Gelder T,Sallustio BCdoi
10.1097/FTD.0b013e31828e8162subject
Has Abstractpub_date
2013-10-01 00:00:00pages
617-23issue
5eissn
0163-4356issn
1536-3694journal_volume
35pub_type
杂志文章abstract::Iron overload resulting from transfusion dependency in some patients with chronic anaemia can be prevented by chelation. Deferasirox is an oral alternative to the well studied but inconvenient deferroxamine therapy. The pharmacokinetic parameters of this new drug suggest potential interindividual variability and patie...
journal_title:Therapeutic drug monitoring
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更新日期:2010-08-01 00:00:00
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journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
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abstract::The objective of this study was to conduct an assessment of patient and parental preferences and an economic analysis of hospital costs in sampling blood and saliva for therapeutic drug monitoring (TDM). Costs and preferences were evaluated in the course of a study, which compared anticonvulsant concentrations in bloo...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199410000-00001
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-198001000-00004
更新日期:1980-01-01 00:00:00
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
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更新日期:2018-10-01 00:00:00
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199410000-00011
更新日期:1994-10-01 00:00:00
abstract::An isocratic high-performance liquid chromatography method with amperometric detection for the assay of plasma salbutamol is described. The plasma extract is injected into the chromatographic system via a loop column. This insures the purification of the injected extracts and allows a simple and rapid liquid-solid ext...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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pub_type: 更正并重新发布的文章,杂志文章
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更新日期:2003-12-01 00:00:00
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更新日期:2017-10-01 00:00:00
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更新日期:2013-06-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2011-04-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Therapeutic drug monitoring
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doi:10.1097/00007691-199704000-00014
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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journal_title:Therapeutic drug monitoring
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更新日期:1991-01-01 00:00:00
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199804000-00016
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198802000-00016
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