Levetiracetam: relative bioavailability and bioequivalence of a 10% oral solution (750 mg) and 750-mg tablets.
Levetiracetam, an antiepileptic drug, is used worldwide as an adjunctive treatment for partial-onset seizures. The availability of a new oral solution formulation would provide an additional treatment option for patients who have difficulty swallowing tablets. A phase I single-center, randomized, open-label, two-way crossover, single-dose study was conducted to confirm that a 10% oral solution of levetiracetam was bioequivalent to the 750-mg oral tablet and to characterize its pharmacokinetics. Each of 24 healthy subjects received a single oral 750-mg dose of the randomized levetiracetam formulation (7.5 mL of 10% solution or 750-mg tablet) on day 1 and a single oral dose of the alternate formulation on day 8. Serial blood samples were collected from 0 to 36 hours after each dose administration for determination of plasma levetiracetam concentrations. Pharmacokinetic parameters were calculated, and bioequivalence of the two formulations was evaluated. The mean levetiracetam plasma concentration-time curves and pharmacokinetic parameters essentially were identical for the oral 10% solution and tablet and consistent with previously reported levetiracetam pharmacokinetics. The 90% confidence limits of the geometric mean ratio of the two formulations for area under the plasma concentration-time curve from time 0 to infinity, area under the plasma concentration-time curve from time 0 to last measurable time point, and maximum plasma concentration were within the 80% to 125% range, demonstrating bioequivalence of the two formulations. Both levetiracetam formulations were well tolerated. The levetiracetam 10% oral solution is a bioequivalent, well-tolerated alternative to the tablet formulation in patients who have difficulty swallowing.
Coupez
René
R
UCB S.A. Parma Sector, Chemin do Foriest, Braine l'Alleud, Belgium.
Straetemans
Roel
R
Sehgal
Geeta
G
Stockis
Armel
A
Lu
Zhihong Sarah
ZS
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D012996:Solutions; D013607:Tablets; D013810:Therapeutic Equivalency
D000927:Anticonvulsants; D012996:Solutions; D013607:Tablets; D000077287:Levetiracetam; D010889:Piracetam