Evaluation of the Pharmacokinetic Interaction Between the Voltage ‐ and Use‐Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers

AbstractVixotrigine is a voltage ‐ and use‐dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate‐glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first‐line treatment for trigeminal neuralgia. We conducted a double‐blind, randomized, placebo‐controlled, parallel‐group, single‐center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in hea lthy volunteers, the safety and tolerability of combined treatment, and PK recovery of vixotrigine following carbamazepine discontinuation. Randomly assigned treatments were carbamazepine (100 mg twice a day, days 1‐3 and 200 mg twice a day, days 4‐21) or placebo on days 1 to 21. All volunteer s received vixotrigine 150 mg 3 times a day on days 16 to 28. At prespecified times, whole‐blood samples were collected for PK assessment. Statistical analyses were performed on the log‐transformed PK parameters area under the concentration‐time curve within a dosing interval (AUC0 ‐tau) and maximum observed concentration (Cmax) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC0 ‐tau and Cmax were reduced by 31.6% and 26.3%, respectively, when coadministered with carbamazepine compared with placebo. Seven days after carbamazepine dis...
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Manuscript Source Type: research