Veterinary drug bioequivalence determination

Abstract

A bioequivalence trial is a statistically based comparison of two formulations to demonstrate with a controlled consumer (patient) risk that two formulated drug products are interchangeable. The basic assumption underlying a bioequivalence trial is that essentially the same plasma time-course leads to essentially the same effect allowing two formulations to be interchanged. Bioequivalence is generally assessed using kinetic end points and in practice, two formulations in which bioavailability parameters (rate and extent) differ by 20% or less, with a 90% degree of confidence, are considered to be bioequivalent. In this review, the design and evaluation of bioequivalence studies are presented with special attention given to scientific issues.

Concentrations of clindamycin hydrochloride in homogenates of normal dog skin when administered at two oral dosage regimens

“…The relatively small number of dogs that have been used and of skin samples that have been obtained (n ¼ 4 or 5 for each sampling day) in this study was selected for ethical (due to the invasiveness of skin biopsy) and was also justified by the crossover study design which decreases the influence of inter-subject differences (Toutain et al 1997). Dogs were fasted for a standard period of 9 h prior to each dosing in order to avoid possible interference from post meal changes in gastrointestinal motility, secretion and blood flow (Toutain et al 1997;Boothe 2001) However, since food does not have a significant impact on the absorption of orally administered clindamycin (Burrows 1980;Harari & Lincoln 1989;Noli & Boothe 1999;Boothe 2001), the results of this study are expected to apply also when this antimicrobial is given on a full stomach.…”

“…Dogs were fasted for a standard period of 9 h prior to each dosing in order to avoid possible interference from post meal changes in gastrointestinal motility, secretion and blood flow (Toutain et al 1997;Boothe 2001) However, since food does not have a significant impact on the absorption of orally administered clindamycin (Burrows 1980;Harari & Lincoln 1989;Noli & Boothe 1999;Boothe 2001), the results of this study are expected to apply also when this antimicrobial is given on a full stomach. The actual dose of clindamycin was not the same as the target dose which is inevitable for tablet formulation and is not expected to interfere with the results because the median actual daily dose was exactly the same for both the dosage regimens.…”

“…Drug concentrations were measured not only during the first but also during the third day of administration in order to reveal a possible accumulation in the skin. The washout period between different dosage regimens should be at least equal to 10 half-lives (Toutain et al 1997). A period of one week was selected on the assumption that the t 1/2 of clindamycin in the skin would be somewhat similar to that in serum which usually ranges from 5 to 6 h (Harari & Lincoln 1989;Lavy et al 1999;Batzias et al 2005) and has never been reported to exceed 10.5 h (Lavy et al 2000).…”

Pharmacokinetics and Bioequivalence of Florfenicol Oral Solution Formulations (Flonicol® and Veterin®10%) in Broiler Chickens

“…In this respect, generic pharmaceutical preparations of florfenicol seeking approval to enter the market should demonstrate their ability to achieve C max and AUC values that are equivalent to that of the original preparation. Inability to maintain high enough concentrations for sufficient periods of time may lead to therapeutic failure and may encourage the proliferation of resistant micro-organisms [19,23]. In this study, the pharmacokinetics and bioequivalence of two oral florfenicol solutions (Flonicol ® and Veterin ® 10%) were investigated in healthy broiler chickens at a dose rate of 20mg/kg bw according to the manufacture's recommendations.…”

“…In order to optimize the clinical outcome and to minimize the development of bacterial resistance, the copied pharmaceutical preparations must be bioequivalent to the innovator product [19,20]. These issues have become an on-going subject of concern within the European Community and the United States of America for registering new and generic drug products [19,[21][22][23].…”