title: Role of pharmacokinetics in establishing bioequivalence for orally inhaled drug products: workshop summary report.
abstract: In April 2010 a workshop on the "Role of Pharmacokinetics in Establishing Bioequivalence for Orally Inhaled Drug Products" was sponsored by the Product Quality Research Institute (PQRI) in coordination with Respiratory Drug Delivery (RDD) 2010. The objective of the workshop was to evaluate the current state of knowledge and identify gaps in information relating to the potential use of pharmacokinetics (PK) as the key indicator of in vivo bioequivalence (BE) of locally acting orally inhaled products (OIPs). In addition, the strengths and limitations of the PK approach to detect differences in product performance compared with in vitro and pharmacodynamic (PD)/clinical/therapeutic equivalence (TE) studies were discussed. The workshop discussed the relationship between PK and lung deposition, in vitro assessment, and PD studies and examined potential PK study designs that could serve as pivotal BE studies. It has been recognized that the sensitivity to detect differences in product performance generally decreases as one moves from in vitro testing to PD measurements. The greatest challenge in the use of PD measurements with some OIPs (particularly inhaled corticosteroids) is the demonstration of a dose-response relationship (for local effects), without which the bioassay, and hence a PD study, may not have sufficient sensitivity to detect differences in product performance. European authorities allow demonstration of in vivo BE of OIPs based solely on pharmacokinetic studies. This workshop demonstrated broader interest among discipline experts and regulators to explore approaches for the use of PK data as the key determinant of in vivo equivalence of locally acting OIPs. If accepted, the suggested approach (PK alone or in conjunction with in vitro tests) could potentially be applied to demonstrate BE of certain orally inhaled drugs.
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877-0368, USA. dennis.oconnor@boehringer-ingelheim.com
authors: Dennis
authors: D
authors: O'Connor
authors: Wallace P
authors: WP
authors: Adams
authors: Mei-Ling
authors: ML
authors: Chen
authors: Peter
authors: P
authors: Daley-Yates
authors: John
authors: J
authors: Davis
authors: Hartmut
authors: H
authors: Derendorf
authors: Murray P
authors: MP
authors: Ducharme
authors: Anders
authors: A
authors: Fuglsang
authors: Myra
authors: M
authors: Herrle
authors: Günther
authors: G
authors: Hochhaus
authors: Susan M
authors: SM
authors: Holmes
authors: Sau L
authors: SL
authors: Lee
authors: Bing V
authors: BV
authors: Li
authors: Svetlana
authors: S
authors: Lyapustina
authors: Stephen
authors: S
authors: Newman
authors: Martin
authors: M
authors: Oliver
authors: Beverley
authors: B
authors: Patterson
authors: Joanne
authors: J
authors: Peart
authors: Guirag
authors: G
authors: Poochikian
authors: Partha
authors: P
authors: Roy
authors: Tushar
authors: T
authors: Shah
authors: Gur Jai Pal
authors: GJ
authors: Singh
authors: Sandra Suarez
authors: SS
authors: Sharp
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004335:Drug and Narcotic Control; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068297:Fluticasone-Salmeterol Drug Combination; D000068759:Formoterol Fumarate; D006801:Humans; D013810:Therapeutic Equivalency
chemical_list: D000730:Androstadienes; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol; D000068759:Formoterol Fumarate