Building a Population Pharmacokinetic Model of Tacrolimus in Paediatric Liver Transplant Patients
试验速览
- 阶段
- 不适用
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Blood concentration of tacrolimus (ng/mL)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Arm 1: Pharmacokinetic and Pharmacogenetic
Liver Transplant Children treated with tacrolimus
干预措施: Pharmacokinetic (Other)
Arm 1: Pharmacokinetic and Pharmacogenetic
Liver Transplant Children treated with tacrolimus
干预措施: Pharmacogenetic (Other)
Arm 1: Pharmacokinetic and Pharmacogenetic
Liver Transplant Children treated with tacrolimus
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Blood concentration of tacrolimus (ng/mL)
时间窗: Between day2 and day4 and day 10 and day14, after day 21
Residual concentration, Cmin, Cmax, Cl/F and Area Under the Curve of tacrolimus (AUC)
次要结局
- "P3A5" cytochrome (CYP3A5/4), "ABCB1" genotypes of donor and recipient.(Up to 3 years)
- Time to achieve two concentrations of tacrolimus in the therapeutic target without change of posology(Up to 3 years)
- Clinical Occurrence of adverse events (reject and/or adverse effects with tacrolimus)(Up to 3 years)
- Factor V and prothrombin time(Up to 3 years)