title: Challenges associated with the demonstration of bioequivalence of intramammary products in ruminants.
abstract: This article explores the numerous challenges encountered when the goal is to demonstrate bioequivalence (BE) between test and reference intramammary (IMM) products in ruminants. Numerous pathophysiological factors of mastitis and physicochemical properties of IMM formulations are implicated in the difficulties in confirming BE for this dosage form. Advantages and disadvantages of current BE study designs are discussed, and alternative perspectives are outlined. Ongoing and future research increasing our knowledge of the pharmacokinetics and pharmacodynamics of antimicrobial drugs delivered through this route is crucial to better understanding the implications of clinically significant formulation differences in the demonstration of BE and may also help in developing more effective IMM formulations for ruminants.
authors.affiliation: Clinical Evaluation Division, Health Canada, Veterinary Drugs Directorate, Ottawa, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Lainesse
authors.forename: R
authors.initials: R
authors.lastname: Gehring
authors.forename: K
authors.initials: K
authors.lastname: Pasloske
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Soback
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: T
authors.initials: T
authors.lastname: Whittem
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004304:Dosage Forms; D004333:Drug Administration Routes; D005260:Female; D006863:Hydrogen-Ion Concentration; D007774:Lactation; D008321:Mammary Glands, Animal; D008413:Mastitis / Q000188:drug therapy*; D008954:Models, Biological; D012107:Research Design / Q000592:standards; D012418:Ruminants; D013810:Therapeutic Equivalency; D019155:Veterinary Drugs / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D004304:Dosage Forms; D019155:Veterinary Drugs