Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C2

Brunet, Mercè; Campistol, J. M.; Millán, Olga; Vidal, Elsie González; Esforzado, Núria; Rojo, Isabel; Jiménez, O.; Oppenheimer, Federico; Corbella, Jacint Corbella i; Martorell, Jaume

doi:10.1016/s1567-5769(03)00097-3

Cited by 26 publications

(19 citation statements)

References 19 publications

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“…Due to the difficulties to obtain blood at several time points, especially in transplant recipients, blood should be analyzed at least at two time points (e.g. before and 2 h after therapy) to provide information about drug efficacy and about the relationship between pharmacodynamics and pharmacokinetics [42]. In a study in stable HTx recipients treated with a combination therapy of CsA plus MMF, we obtained a high correlation between CsA effects and both blood CsA concentrations and CsA dose.…”

Section: Clinical Studiesmentioning

confidence: 97%

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Barten¹,

Gummert²

2007

Transfus Med Hemother

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Conventional therapeutic drug monitoring based on measuring of blood concentrations (pharmacokinetic) is important in the clinical management of immunosuppressive therapy in transplantation medicine. Since rejection or infection occurs at irregular drug concentrations, immunosuppressive drug therapy is often empiric and prophylactic in nature. In addition, blood immunosuppressant levels are only indirect predictors of the pharmacologic effects on immune cells (pharmacodynamic) because, due to the genetic heterogeneity, the immune systems of the transplant recipients are not equally sensitive to drug effects. Therefore, therapeutic drug monitoring requires the application of reliable and effective methods to study the pharmacodynamic variability by direct measurements of drugs effects on immune cell functions. Against this background we developed assays which are based on whole blood, flow cytometry and biomarkers of diverse functions of T cells and of dendritic cell subsets. These biomarker assays allow us to differentiate between synergistic and antagonistic pharmacodynamic effects of an immunosuppressive drug combination therapy in vitro and to predict the pharmacodynamic drug effects in heart-transplanted recipients. Such a pharmacodynamic drug monitoring based on biomarkers may offer the opportunity to complete conventional therapeutic drug monitoring and, therefore, to tailor immunosuppressive therapy more individually.

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Section: Clinical Studiesmentioning

confidence: 97%

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Barten¹,

Gummert²

2007

Transfus Med Hemother

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“…However, the most important question is whether the CVs are comparable when they are obtained by different methods. Brunet et al (15 ) did not describe in detail how they obtained the CV; therefore, a direct comparison is not possible. Caruso et al (6 ) reported CVs of 4% in samples with high CaN activity and 12% in samples with low CaN activity.…”

Section: Discussionmentioning

confidence: 99%

Validation of the Calcineurin Phosphatase Assay

2004

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“…Studies have shown that the measurement of multiple samples and determination of the area under curve (AUC) may be a better indicator of patient transplant success. However, obtaining true AUC is difficult; therefore, a testing scheme has been proposed that uses the measurement of CsA 2 H after dose (C2 monitoring or CsA extended range testing) [5][6][7]. This scheme has been optimized and evolved to monitor a single sample at 2 H with the introduction of CsA microemulsion (Neoral R ) [8].…”

Section: Introductionmentioning

confidence: 99%

The Emit® 2000 Cyclosporine Specific Assay, Extended Range: Development of an application protocol for the V‐Twin® Analyzer

Morjana

Yau

Rea

et al. 2011

Biotech and App Biochem

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We evaluated a new protocol for measurement of cyclosporine A (CsA) 2 H after dose (C2) on the V-Twin® analyzer. Imprecision, recovery, and linearity were determined using CsA-spiked blood pools. Accuracy was evaluated using specimens from renal, cardiac, and liver transplant patients, and results were compared with those from liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the Abbott TDx®/TDxFLx® assay. Cross-reactivity and interferences were assessed in the presence of 800 ng/mL CsA. Imprecision coefficients of variation were 3.3%-4.8% (within run) and 5.9%-8.7% (total). Recovery was within 10% of the expected values. Linearity was 350-2,000 ng/mL. Calibration was stable for ≥ 2 weeks. Method comparison showed regression statistics: V-Twin® = 1.01 × LC tandem MS + 36.1, r = 0.971; V-Twin® = 1.13 × Abbott - 92.4, r = 0.969. Metabolite cross-reactivity and interference (endogenous substances and drugs) were within ±10%. The C2 protocol on the V-Twin® analyzer provides acceptable assay performance and accurate determination of whole blood CsA drawn at 2 H after dose.

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Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C2

Cited by 26 publications

References 19 publications

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Biomarkers in Transplantation Medicine: Prediction of Pharmacodynamic Drug Effects

Validation of the Calcineurin Phosphatase Assay

The Emit® 2000 Cyclosporine Specific Assay, Extended Range: Development of an application protocol for the V‐Twin® Analyzer

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