Immunosuppressive Therapy Optimization: Development of a Population Pharmacokinetic-pharmacodynamic (PK-PD) Model in Liver Transplantation

Study Overview
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Brief Summary
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Prospective, non-randomized, open Pharmacokinetic-Pharmacogenetic-Pharmacodynamic monocentric study. Donor and recipient CYP3A5 genotype and recipient ABCB1 will not be communicate to clinicians or patients during the study.

Official Title
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Immunosuppressive Therapy Optimization: Development of a Population Pharmacokinetic-pharmacodynamic (PK-PD) Model in Liver Transplantation

Conditions
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Liver Transplantation

Intervention / Treatment
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* Other: Pharmacokinetic-pharmacodynamic model in liver transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults over 18 Liver transplant recipients Treated with an immunosuppressive protocol with tacrolimus Informed on the study and who did not refuse to participate Exclusion Criteria: Patients who participate in a study with procedures incompatible with the present study. Patients with legal protection/deprived of liberty.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Pharmacokinetic-pharmacodynamic model in liver transplantation|Biological: tacrolimus and calcineurin dosage, donor and recipient CYP3A5 and ABCB1 genotypes determination|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prediction of calcineurin inhibition, responsible for the immunosuppressive effect | Assessement of the relationships between tacrolimus dosage, whole-blood and intracellular concentrations | Week 24 | 
| Prediction of calcineurin inhibition, responsible for the immunosuppressive effect | Assessement of the relationships between intracellular concentrations of tacrolimus and calcineurin activity | Week 24 | 
| Prediction of calcineurin inhibition, responsible for the immunosuppressive effect | Assessement of the relationships between donor and recipient CYP3A5 and ABCB1 genotypes and dose/concentration of tacrolimus | Week 24 | 
| Prediction of calcineurin inhibition, responsible for the immunosuppressive effect | Assessement of the relationships between intracellular concentration of tacrolimus and/or calcineurin activity and ACR, in patients treated with immediate release or modified-release formulation of tacrolimus | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study of impact of pharmacogenetic and demographic data on tacrolimus intracellular concentration |  | Week 24 | 
| Evaluation of the role of the measurement of intracellular concentration as a longitudinal biomarker in preventing acute cellular graft (ACR) |  | Week 24 | 
| Study of variability of tacrolimus intracellular concentration according to its pharmaceutic form (immediate or sustained release) |  | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, pharmacodynamic, tacrolimus, CYP3A5, liver transplantation