A Phase I study of the pharmacokinetics (PK), bioavailability, dose proportionality, safety, and tolerability of topiramate injection compared to Oral topiramate in healthy adult participants.

内容摘要

This Phase I study evaluated the safety, tolerability, and pharmacokinetics of a 30-min topiramate injection (intravenous [IV] TPM) infusion compared with oral topiramate (oral TPM) in healthy adult participants. In this randomized, open-label, dose escalation, crossover study with 37 healthy participants received single doses of 50, 100, or 200 mg of an oral TPM tablet and an IV TPM formulation, using sulfobutylether beta-cyclodextrin as a solubilizer and stabilizer, infused over 30 min, with a 12-day washout. Blood samples for pharmacokinetic assessments were collected at predose through 192 h post dose. Concentration-time data were analyzed using non-compartmental analysis, and IV TPM relative bioavailability was determined. Topiramate injection AUCinf (total exposure) increased linearly with dose. The mean (90% confidence interval [CI]) relative bioavailability was 97.1% (94.6-99.7%). The mean (± SD) clearance for 50, 100, and 200 mg IV TPM was 1.4 L/h (±0.2), 1.3 L/h (±0.2), and 1.3 L/h (±0.2), respectively. Half-life was comparable across routes. Dose proportionality was demonstrated for AUCinf over the 50-200 mg range. No serious adverse events were reported. These findings suggest that when oral TPM administration is not feasible, equivalent doses of topiramate injection infused over 30 min at intervals can temporarily replace oral dosing until it can be resumed.