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Prospective and monocentric pharmacokinetic study
Membrane transporters supporting tacrolimus at the lymphocyte level may play a role in the variability of the relationship between tacrolimus blood concentration and intracellular concentration, or may be the main explanatory factors. Nevertheless, most of the studies carried out on the subject, have been by genetic approach, neglecting in fact the membrane expression of these transporters, which could testify more to the real effect on the transport of tacrolimus. A better understanding of the cellular transport mechanisms of tacrolimus in the T lymphocyte could thus make it possible to identify sub-populations of patients under-exposed at the intra-lymphocyte level, despite satisfactory systemic exposure.
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| Measure | Description | Time Frame |
|---|---|---|
| Correlation between drug transporters expression (RNA and protein) in PBMC and tacrolimus intra-PBMC concentration | The mRNA levels will be recorded as a cycle threshold difference between the studied gene, and the mean of two housekeeping genes (ACTB and B2M). The proteic expression of the studied transporters will be recorded as fluorescent intensity levels | During the consultation (between 2 and 24 months after the transplant) |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between drug transporters RNA expression in PBMC and drug transporters protein expression in PBMC | The mRNA levels will be recorded as a cycle threshold difference between the studied gene, and the mean of two housekeeping genes (ACTB and B2M). The proteic expression of the studied transporters will be recorded as fluorescent intensity levels | During the consultation (between 2 and 24 months after the transplant) |
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Inclusion Criteria:
Exclusion Criteria:
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Hepatic and / or renal transplantation
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| Name | Affiliation | Role |
|---|---|---|
| Florian LEMAITRE | Rennes University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rennes University Hospital | Rennes | 35033 | France |
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| Correlation between tacrolimus blood to intracellular ratio and adverse events. | Tacrolimus-related adverse effects as recorded on the medical record of the patient. | During the consultation (between 2 and 24 months after the transplant) |
| Correlation between tacrolimus intra-PBMC concentration and treatment outcome | Treatment outcome as recorded on the medical record of the patient. | During the consultation (between 2 and 24 months after the transplant) |
| Correlation between tacrolimus intra-PBMC concentration and comedications | Co-medications as recorded on the medical record of the patient. | During the consultation (between 2 and 24 months after the transplant) |
| Correlation between tacrolimus intra-PBMC concentrations and Donor Graft cell-free DNA (cf-DNA) concentration | Donor graft cf-DNA characterized the cell death marker, released from necrotic or apoptotic cells in the transplant organ, and may therefore be useful as a marker for graft injury. When its plasma concentration increases, it evidences that a lesion process occurs in the graft | During the consultation (between 2 and 24 months after the transplant) |