title: Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.
abstract: Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers.
authors: Faculty of Medicine, Institute of Preclinical and Clinical Pharmacology & Toxicology, Skopje, Republic of Macedonia.
authors: Marija
authors: M
authors: Petruševska
authors: SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana, 1529, Slovenia.
authors: Sandra
authors: S
authors: Berglez
authors: SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana, 1529, Slovenia.
authors: Igor
authors: I
authors: Krisch
authors: SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana, 1529, Slovenia.
authors: Igor
authors: I
authors: Legen
authors: SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana, 1529, Slovenia.
authors: Klara
authors: K
authors: Megušar
authors: SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana, 1529, Slovenia.
authors: Luka
authors: L
authors: Peternel
authors: AstraZeneca Pharmaceutics, R&D, Mölndal, Sweden.
authors: Bertil
authors: B
authors: Abrahamsson
authors: Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil.
authors: Rodrigo
authors: R
authors: Cristofoletti
authors: RIVM (National Institute for Public Health and the Environment), Bilthoven, The Netherlands.
authors: D W
authors: DW
authors: Groot
authors: World Health Organization, Geneva, Switzerland.
authors: Sabine
authors: S
authors: Kopp
authors: Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg - University, Mainz, Germany.
authors: Peter
authors: P
authors: Langguth
authors: Center for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Maryland.
authors: Mehul
authors: M
authors: Mehta
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland.
authors: James E
authors: JE
authors: Polli
authors: International Pharmaceutical Federation (FIP), The Hague, The Netherlands.
authors: Vinod P
authors: VP
authors: Shah
authors: Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors: Jennifer
authors: J
authors: Dressman
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001702:Biopharmaceutics / Q000145:classification; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D006801:Humans; D000077287:Levetiracetam; D010539:Permeability; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D000927:Anticonvulsants; D004304:Dosage Forms; D000077287:Levetiracetam; D010889:Piracetam
keywords: absorption; bioavailability; bioequivalence; biopharmaceutical classification system (BCS); biowaiver; levetiracetam; permeability; pharmacokinetics; solubility