TY - JOUR T1 - Influence on Busilvex® Pharmacokinetics of Clonazepam Compared to Previous Phenytoin Historical Data JF - Anticancer Research JO - Anticancer Res SP - 2977 LP - 2984 VL - 30 IS - 7 AU - E. CARRERAS AU - J.Y. CAHN AU - C. PUOZZO AU - N. KRÖGER AU - G. SANZ AU - A. BUZYN AU - A. BACIGALUPO AU - J.P. VERNANT Y1 - 2010/07/01 UR - http://ar.iiarjournals.org/content/30/7/2977.abstract N2 - 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 (coeffiecient 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. ER -