Bioequivalence of a Novel Minitablet Formulation of Levetiracetam

Abstract

Background:

To investigate whether rapidly dissolving levetiracetam minitablets are bioequivalent to a single tablet of the same strength.

Methods:

2 bioequivalence studies were carried out investigating the 1 000 mg and 1 500 mg strength of such novel medicinal products relative to single-unit film-coated originator tablets for reference. In each study, 16 young healthy subjects (8 males, 8 females) were investigated according to a 2,2,2-cross-over design with 1 week between periods for washout purposes. Each time, the plasma pharmacokinetics were profiled for 36 h after dosing.

Results:

There were no relevant differences between the formulations with regard to t_max, apparent terminal half-life and the mean residence time. For the 1 000 mg strength, the estimated ratios of the true treatment means for test to reference were 1.008 (90% CI: 0.897–1.133), 1.010 (90% CI: 0.964–1.057), and 1.012 (90% CI: 0.965–1.062) for C_max, AUC_(0–tz), and AUC_(0–∞), respectively; for the 1 500 mg strength, the respective ratio estimates were 0.960 (90% CI: 0.892–1.034), 1.005 (90% CI: 0.971–1.040), and 1.006 (90% CI: 0.970–1.042).

Conclusions:

Rapidly dissolving levetiracetam minitablets are bioequivalent with the originator single-unit reference tablets. Such alternative medicinal products make it easier and more convenient to individualise treatment of patients with epilepsy eligible to treatment with levetiracetam, particularly at higher doses when single-unit tablets, by being very large are difficult to swallow.

Key words

levetiracetam - pharmacokinetics - bioequivalence

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