Bioequivalence study of the antiepileptic drug levetiracetam in concentrated solution for injection versus oral tablets in healthy Chinese subjects under fasting conditions: A randomized, open-label, three-way crossover study

摘要

Objective: The objective of this study was to evaluate the bioequivalence between single-dose intravenous (IV) infusion injection (the infusion time was 15 minutes and 45 minutes) and tablets of 1,000 mg levetiracetam in healthy Chinese male subjects. Materials and methods: This was a randomized, open-label, three-way crossover bioequivalence study. All of the 24 healthy male subjects received a treatment of 45-minute IV infusion, 15-minute IV infusion, and oral tablets. Results: After a single dose, the AUC, V-d, Cl. and T-1/2 were all essentially consistent among the treatment; t(max )of 15-minute IV, 45-minute IV, and oral tablets were 0.25 hours, 0.75 hours, and 0.5 hours, respectively. The C(max )of the 15-minute IV was higher than the value of the 45-minute IV and the oral tablets. The geometric mean of the 15-minute IV/oral and the 45-minute IV/oral ratios were 101.02% (90% CI, 98.95 - 103.12) and 98.22% (90% CI, 96.22 - 100.27), respectively, for AUC(0-t). And those for C-max were 169.09% (90% CI, 155.21 - 184.21) and 106.95 (90% CI, 98.20 - 116.48), respectively. There were no severe adverse events or other adverse events with clinical significance during the study. Conclusion: In these healthy subjects. the results showed that 45-minute IV and oral tablets were bioequivalent. The t(max) of the 15-minute IV and oral tablets were significantly different. The t(max) of the oral tablets was between that of the 15-minute IV and the 45-minute IV. The elimination of injection and oral tablets in humans was similar. Levetiracetam concentrated solution for injection and oral tablets were safe for healthy Chinese male subjects in this study.