1. Influence on Busilvex® pharmacokinetics of clonazepam compared to previous phenytoin historical data
- Author
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Carreras, E., Cahn, J. Y., Puozzo, C., Kröger, N., GUILLERMO SANZ, Buzyn, A., Bacigalupo, A., Vernant, J. P., TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Recherche Pierre Fabre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
Male ,Transplantation Conditioning ,MESH: Busulfan ,MESH: Drug Interactions ,MESH : Transplantation Conditioning ,MESH : Prospective Studies ,MESH : Alkylating Agents ,Clonazepam ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,MESH: Clonazepam ,Drug Interactions ,MESH : Female ,Prospective Studies ,MESH : Busulfan ,MESH : Immunosuppressive Agents ,MESH : Cyclophosphamide ,MESH: Transplantation Conditioning ,MESH : Seizures ,MESH: Middle Aged ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,MESH : Adult ,MESH: Seizures ,MESH: Alkylating Agents ,MESH: Young Adult ,Hematologic Neoplasms ,Anticonvulsants ,Female ,MESH: Immunosuppressive Agents ,MESH : Hematologic Neoplasms ,Immunosuppressive Agents ,Adult ,MESH : Anticonvulsants ,Alkylating Agents ,Adolescent ,MESH : Male ,MESH : Young Adult ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Young Adult ,MESH: Anticonvulsants ,Seizures ,MESH : Adolescent ,MESH : Hematopoietic Stem Cell Transplantation ,Humans ,MESH : Middle Aged ,Busulfan ,Cyclophosphamide ,MESH: Hematopoietic Stem Cell Transplantation ,MESH: Adolescent ,MESH: Humans ,MESH : Humans ,MESH: Cyclophosphamide ,MESH: Adult ,MESH: Male ,MESH: Prospective Studies ,MESH : Clonazepam ,MESH : Drug Interactions ,MESH: Phenytoin ,Phenytoin ,MESH: Female ,MESH : Phenytoin ,MESH: Hematologic Neoplasms - Abstract
International audience; This study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg) was administered every six hours during four consecutive days. Clonazepam (0.025 to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least 12 hours prior to i.v. Bu dosing and continued until 24 hours after the last dose. Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis. Through population PK analysis, a 10% average increase (coefficient of variation, RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with clonazepam as compared to phenytoin, which was considered as not being clinically relevant. The suspected induction on Bu metabolism by phenytoin should have resulted in the opposite effect. The patient efficacy and safety profiles were comparable between the two cohorts.