Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The main objective is to develop pharmacokinetic methods for individual dose adjustment of the global immunosuppressive treatment (cyclosporine, tacrolimus, mycophenolate mofetil and everolimus, taking into account the pharmacokinetic interactions), in order to optimise the efficiency and reduce the potentially severe sides effects of these drugs.
Forty five heart-transplant patients are to be included in this phase IV study to obtain a minimum of 10 patients treated with tacrolimus-mycophenolate, 10 with cyclosporine-mycophenolate and 20 with everolimus-cyclosporine.
Ten to 11 blood samples will be collected within the 8 to 12 hours post-dose in each patient and the immunosuppressive drug concentrations will be measured by LC-MS/MS.
The pharmacokinetic models and Bayesian estimators thus developed will provide tools for individual dose adjustment of immunosuppressive drugs simultaneously, at different post-transplant periods, using the area under the concentration-time curve (AUC) estimated using a limited number of time-points (2 or 3).
For each heart transplant patient, 10 to 11 blood samples (5 mL each) will be collected following dosing of he immunosuppressive drugs (at T0, T20', T40', T60', T90', T2h, T3h, T4h, T6h, T8h and T10h + T12h for inpatients), at several post-transplant periods (7 to 15 days, 1 month, 3 month and 1 year after transplantation). One more blood sample will be taken at D7-14 for pharmacogenetic analyses.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cyclosporine, tacrolimus, mycophenolate mofetil and everolimus (immunosuppressive drugs) | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs. |
| Measure | Description | Time Frame |
|---|---|---|
| Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters. | ||
| Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pierre MARQUET, MD | University Hospital, Limoges | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux | Bordeaux | France | ||||
| CHU de Clermont-Ferrand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26192348 | Result | Woillard JB, Saint-Marcoux F, Monchaud C, Youdarene R, Pouche L, Marquet P. Mycophenolic mofetil optimized pharmacokinetic modelling, and exposure-effect associations in adult heart transplant recipients. Pharmacol Res. 2015 Sep;99:308-15. doi: 10.1016/j.phrs.2015.07.012. Epub 2015 Jul 17. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Clermont-Ferrand |
| France |
| CHU de Lille | Lille | France |
| CHU de Limoges | Limoges | France |
| Hôpital Louis Pradel - CHU de Lyon | Lyon | France |
| CHU de Nantes | Nantes | France |
| Hôpital Européen Georges Pompidou | Paris | France |
| Hôpital Pitié-Salpêtrière | Paris | France |
| CHU de Rennes | Rennes | France |
| CHU de Rouen | Rouen | France |
| CHU de Strasbourg | Strasbourg | France |
| CHU de NANCY | Vandœuvre-lès-Nancy | France |
| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| D000068338 | Everolimus |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D020123 | Sirolimus |
Not provided
Not provided