Impact of Drug Interactions on Clobazam and N-Desmethylclobazam Concentrations in Pediatric Patients With Epilepsy

This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. Methods: This was a retrospective chart review including patients older than 1 month, who received CLB between April 2012 and March 2017. Extracted data included patient demographics, CLB daily dose, CLB and NCLB Cp, calculated CLB and NCLB Cp/Cp and Cp/D ratios, and all concomitant drugs. Results: The study included 995 CLB concentration sets from 302 patients (median age 7.6 years and range 0.2–40.1 years). Pharmacokinetic variability was extensive, as seen by widespread ranges of CLB and NCLB Cp, NCLB/CLB Cp ratio, and 3 Cp/D ratios (CLB, NCLB, and CLB + NCLB). Comedications, described as CYP3A4 inducers and/or CYP2C19 inhibitors (carbamazepine, eslicarbazepine, felbamate, (fos)phenytoin, oxcarbazepine, pentobarbital, phenobarbital, rufinamide, and topiramate), generally increased NCLB/CLB Cp ratio (267%–400%), NCLB Cp/D ratio (167%–202%), and CLB + NCLB Cp/D ratio (142%–185%) and decreased CLB Cp/D ratio (47%–76%) compared with a group of concentration sets in patients receiving only neutral comedications (P
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research