Pharmacokinetic of Tacrolimus in Paediatric Liver Transplant Patients (TACTHEP)

Assistance Publique - Hôpitaux de Paris

Status

Unknown

Conditions

Liver Transplantation, Child

Treatments

Other: Pharmacokinetic

Drug: Tacrolimus

Other: Pharmacogenetic

Study type

Interventional

Funder types

Other

Identifiers

NCT02337036

P120904

2013-000948-26 (EudraCT Number)

Details and patient eligibility

About

Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. This study is designed to assess the posology of tacrolimus in post-transplantation in the month after liver transplantation to obtain a therapeutic target between 10-15 ng/mL and the impact of biological and genetic factors on the pharmacokinetic parameters in paediatric liver transplant recipients.

Full description

Tacrolimus is the cornerstone immunosuppressant in children with liver transplantation, its use is complicated by its narrow therapeutic index and variable pharmacokinetics. Therapeutic drug monitoring (TDM) of tacrolimus, based on whole-blood trough concentration (C0) values, is mandatory for use of twice-daily tacrolimus (Prograf_) as in order to decrease interindividual variability in exposure and thereby minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).

Until now, the C0 is the easiest means of individual dose adjustment, as only one blood sample is required and the clinician can easily calculate the dose needed to reach the target. Many factors have an impact on the pharmacokinetic parameters. However the adaptation of the time to achieve the target stays an issue. Among factors of inter and intra variability of pharmacokinetic of tacrolimus, some of them are specific of the pediatric liver transplantation population.

Aims: To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.

Enrollment

80 estimated patients

Sex

All

Ages

6 months to 12 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age of children who need to have a liver transplantation : between 6 month and 12 years
Formulary of consent signed by the two parents.
Children who need to receive tacrolimus per os (Modigraf® ) only after liver transplantation associated to Simulect® (basilixumab) in post-transplantation immediately as main
Affiliation to the system of social protection.

Exclusion criteria

Children who need a multi organs transplantation
Hypersensibility or Contraindication to Modigraf® or others macrolides.
Patients retransplanted in the 14 days after the transplantation
Patients with multivisceral failure
Patients who have an introduction of tacrolimus 3 days after transplantation
Patients who need complementary immunosuppressive drugs with corticoids excepted methylprednisolone used for reject
Patients who received Prograf® per os or iv.
Patients who received Cellcept® or Myfortic®
Opposition to sign the formulary of consent or the understand the note of information