| Přispěvatelé: |
Marquet, Pierre, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Service de Chirurgie Cardiovasculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Chirurgie Cardio-Vasculaire, CHU Strasbourg-Nouvel Hôpital Civil, The PIGREC study was funded by Roche Pharma France, Novartis France and the Limoges University Hospital. |
| Popis: |
Background and objectives: Therapeutic drug monitoring of ciclosporin has been recognized as an essential tool in the management of allograft transplant recipients, as it could help improve their outcome. However, there is still no consensus about the optimal method for monitoring ciclosporin after thoracic transplantation. Better knowledge of the pharmacokinetics of ciclosporin in thoracic transplant patients and design of tools dedicated to ciclosporin monitoring could help its practice and its outcome in this population of patients. The aims of this study were: (i) to investigate the population pharmacokinetics of ciclosporin in thoracic (heart or lung) transplant patients, and study the influence of a range of potential covariates, including demographic, clinical and genetic factors, on pharmacokinetic parameters; and (ii) to develop a Bayesian estimator able to predict the individual pharmacokinetic parameters and exposures indices in this population of patients. Methods: The analysis was performed with 187 full pharmacokinetic profiles obtained in 57 lung and 19 heart transplant patients within the first year post-transplantation. A population pharmacokinetic model was developed by nonlinear mixed effect modeling using NONMEM (version 7.1) from an index dataset (118 profiles). On the basis of this population model and a limited number of blood samples, a Bayesian estimator able to determine ciclosporin area under the blood concentration-time curve during a dosage interval was built and evaluated in the validation dataset (69 profiles). Results: Ciclosporin pharmacokinetics was described using a two-compartment model with time-lagged first order absorption and first order elimination. The final population model included sex as a covariate: ciclosporin apparent oral clearance was on average 37% faster in male than in female patients (34.8 vs 25.4 L/h, p |
