Pharmacokinetics, safety and bioequivalence of intravenous and oral formulations of the antiepileptic drug levetiracetam in healthy Chinese volunteers

doi:10.5246/jcps.2018.11.078

Abstract

Abstract:

The intravenous formulation of levetiracetam (LEV) has been available in clinical practice worldwide for several years, but not in China. In the present study, we aimed to evaluate the bioequivalence of intravenous and oral LEV (tablet), an antiepileptic drug, in healthy Chinese volunteers. Two randomized, single-dose (1500 mg), open-label, 2-period crossover trials were conducted as follows: study A, 15-min infusion; study B, 45-min infusion. A total of 22 healthy men participated in study A, and 24 healthy men and woman were enrolled in study B. In study A, blood samples were collected after termination of each treatment. In study B, samples were collected after oral or after the start of the intravenous administration. Safety and the ratio of intravenous/oral LEV for AUC_0–t and C_max were evaluated. The 90% confidence intervals of C_max and AUC_0–t ratios for LEV 1500-mg tablets versus 15-min intravenous administration were outside the bioequivalence limits (80.00%–125.00%). For LEV 45-min intravenous administration, bioequivalence versus 1500-mg tablets was within the range for C_max and AUC_0–t. The most frequently adverse event (AE) was somnolence. A total of eight subjects experienced nine mild AEs in study A, and 19 subjects experienced 29 mild AEs in study B. Intravenous infusions (15 and 45 min) of 1500-mg LEV were as well tolerated as the oral tablet. Bioequivalence was demonstrated by 45-min infusions. Therefore, direct conversion from oral to intravenous LEV 1500 mg (45-min infusion), or vice versa, was possible.

Key words: Levetiracetam, Epilepsy, Intravenous formulation, Bioequivalence, Safety and tolerability

CLC Number:

R969.1

Supporting:

Lanlan Hu, Juan Zhou, Huan Zou, Yue Zhang, Jianlin Tang. Pharmacokinetics, safety and bioequivalence of intravenous and oral formulations of the antiepileptic drug levetiracetam in healthy Chinese volunteers[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(11): 777-786.

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