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Open Access Research

Endomyocardial, intralymphocyte, and whole blood concentrations of ciclosporin A in heart transplant recipients

Ida Robertsen1*, Pål Falck1, Arne K Andreassen2, Nina K Næss1, Niclas Lunder3, Hege Christensen1, Lars Gullestad2 and Anders Åsberg1

Author Affiliations

1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, Oslo, 0316, Norway

2 Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway

3 Center of Psychopharmacology, Diakonhjemmet Hospital, Oslo, 0319, Norway

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Transplantation Research 2013, 2:5  doi:10.1186/2047-1440-2-5

Published: 8 April 2013

Abstract

Background

In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections. Previous studies indicate that intracellular ciclosporin A (CsA) concentration may be a sensitive acute rejection marker in renal transplant recipients. The aims of this study were to evaluate the relationships between CsA concentrations at different target sites as potential therapeutic drug monitoring (TDM) tools in heart transplant recipients.

Methods

Ten heart transplant recipients (8 men, 2 women) on CsA-based immunosuppression were enrolled in this prospective single-center pilot study. Blood samples were obtained once to twice weekly up to 12 weeks post-transplant. One of the routine biopsies was allocated to this study at each sampling time. Whole blood, intralymphocyte, and endomyocardial CsA concentrations were determined with validated HPLC-MS/MS-methods. Mann–Whitney U test was used when evaluating parameters between the two groups of patients. To correlate whole blood, intralymphocyte, and endomyocardial CsA concentrations linear regression analysis was used.

Results

Three patients experienced mild rejections. In the study period, the mean (range) intralymphocyte CsA trough concentrations were 10.1 (1.5 to 39) and 8.1 (1.3 to 25) ng/106 cells in the rejection and no-rejection group, respectively (P=0.21). Corresponding whole blood CsA concentrations were 316 (153 to 564) and 301 (152 to 513) ng/mL (P=0.33). There were no correlations between whole blood, intralymphocyte, or endomyocardial concentrations of CsA (P >0.11).

Conclusions

The study did not support an association between decreasing intralymphocyte CsA concentrations and acute rejections. Further, there were no association between blood concentrations and concentrations at sites of action, potentially challenging TDM in these patients.

Keywords:
Ciclosporin A; Endomyocardial biopsies; Heart transplantation; Acute rejection; T-lymphocytes