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

Robertsen I, Falck P, Andreassen AK, Næss NK, Lunder N, Christensen H, Gullestad L, Asberg A - Transplant Res (2013)

Bottom Line: In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P,O, Box 1068, Blindern, Oslo, 0316, Norway. ida.robertsen@farmasi.uio.no.

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.

No MeSH data available.


Related in: MedlinePlus

The ratio (± SEM) of whole blood to intralymphocytic CsA trough concentration days after transplantation. (A) The CsA whole blood/intracellular ratio (± SEM) for the three rejection patients. The arrows mark the point where the patients experienced an acute rejection episode. High levels of the ratio represent a drop in intracellular CsA concentration compared to whole blood concentration. (B) The mean whole blood/intracellular ratio (± SEM) for the patients with no rejection.
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Figure 2: The ratio (± SEM) of whole blood to intralymphocytic CsA trough concentration days after transplantation. (A) The CsA whole blood/intracellular ratio (± SEM) for the three rejection patients. The arrows mark the point where the patients experienced an acute rejection episode. High levels of the ratio represent a drop in intracellular CsA concentration compared to whole blood concentration. (B) The mean whole blood/intracellular ratio (± SEM) for the patients with no rejection.

Mentions: Figure 2 shows the individual ratio of whole blood to intralymphocytic CsA concentration for the three patients experiencing rejection and for the mean ratios for the no-rejection patients during the study period. One of the rejection patients (patient 21) showed an increase in the whole blood/intracellular ratio at time of rejection, due to a combination of declined intracellular concentration and a slight increase in the whole blood concentration. In the two other rejection patients (patients 25 and 29) no change was observed in the whole blood/intracellular ratio in conjunction to the rejection episode, but interestingly patient 25 showed substantially increased ratio on several occasions prior to the rejection episode as compared to the mean ratio for the no-rejection group (Figure 2A). In the no-rejection group the mean individual whole blood/intracellular ratio ranged from 33.6 to 86.4 with a corresponding standard deviation range of 17.8 to 46.7. The absolute average intracellular CsA concentration to the time of rejection was 10.4 (1.5 to 39) ng/106 cells in the rejection group and the corresponding average CsA concentration to the mean time of rejection (day 58) was 8.2 (1.3 to 25) ng/106 the no-rejection group (P=0.38). At the rejection day the absolute intracellular CsA concentration for the three rejecting patients were 9.4, 7.2, and 18. 4 ng/106 cells.


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

Robertsen I, Falck P, Andreassen AK, Næss NK, Lunder N, Christensen H, Gullestad L, Asberg A - Transplant Res (2013)

The ratio (± SEM) of whole blood to intralymphocytic CsA trough concentration days after transplantation. (A) The CsA whole blood/intracellular ratio (± SEM) for the three rejection patients. The arrows mark the point where the patients experienced an acute rejection episode. High levels of the ratio represent a drop in intracellular CsA concentration compared to whole blood concentration. (B) The mean whole blood/intracellular ratio (± SEM) for the patients with no rejection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643826&req=5

Figure 2: The ratio (± SEM) of whole blood to intralymphocytic CsA trough concentration days after transplantation. (A) The CsA whole blood/intracellular ratio (± SEM) for the three rejection patients. The arrows mark the point where the patients experienced an acute rejection episode. High levels of the ratio represent a drop in intracellular CsA concentration compared to whole blood concentration. (B) The mean whole blood/intracellular ratio (± SEM) for the patients with no rejection.
Mentions: Figure 2 shows the individual ratio of whole blood to intralymphocytic CsA concentration for the three patients experiencing rejection and for the mean ratios for the no-rejection patients during the study period. One of the rejection patients (patient 21) showed an increase in the whole blood/intracellular ratio at time of rejection, due to a combination of declined intracellular concentration and a slight increase in the whole blood concentration. In the two other rejection patients (patients 25 and 29) no change was observed in the whole blood/intracellular ratio in conjunction to the rejection episode, but interestingly patient 25 showed substantially increased ratio on several occasions prior to the rejection episode as compared to the mean ratio for the no-rejection group (Figure 2A). In the no-rejection group the mean individual whole blood/intracellular ratio ranged from 33.6 to 86.4 with a corresponding standard deviation range of 17.8 to 46.7. The absolute average intracellular CsA concentration to the time of rejection was 10.4 (1.5 to 39) ng/106 cells in the rejection group and the corresponding average CsA concentration to the mean time of rejection (day 58) was 8.2 (1.3 to 25) ng/106 the no-rejection group (P=0.38). At the rejection day the absolute intracellular CsA concentration for the three rejecting patients were 9.4, 7.2, and 18. 4 ng/106 cells.

Bottom Line: In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P,O, Box 1068, Blindern, Oslo, 0316, Norway. ida.robertsen@farmasi.uio.no.

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.

No MeSH data available.


Related in: MedlinePlus