RT Journal Article SR Electronic T1 Influence on Busilvex® Pharmacokinetics of Clonazepam Compared to Previous Phenytoin Historical Data JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2977 OP 2984 VO 30 IS 7 A1 E. CARRERAS A1 J.Y. CAHN A1 C. PUOZZO A1 N. KRÖGER A1 G. SANZ A1 A. BUZYN A1 A. BACIGALUPO A1 J.P. VERNANT YR 2010 UL http://ar.iiarjournals.org/content/30/7/2977.abstract AB 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.