title: Similar in vitro drug release as a surrogate of therapeutic equivalence of locally acting gastrointestinal products--what is the right in vitro method?
abstract: There is--apart from clinical trials--an ongoing discussion on how to demonstrate therapeutic equivalence for locally applied and locally acting products in the gastrointestinal tract. Possibly, among other alternatives, in vitro drug release models could be considered surrogates of drug release and availability at the site of action. However, to date the conditions in which in vitro models provide valid surrogates of in vivo release and availability at the site of action would have to be defined. To demonstrate the potential applicability of in vitro test methods for screening therapeutic equivalence of locally applied and locally acting gastrointestinal products and also to get an idea of which would be the right dosage form for an individual patient a series of in vitro studies was performed comparing a variety of in vitro release methods ranging from pharmacopoeial methods to "patient-specific" release methods in examining drug release of four mesalazine tablet formulations intended for local drug delivery in the gastrointestinal tract. Results from this study indicated that pharmacopoeial quality control methods are hardly applicable to predict the therapeutic equivalence of such products. Moreover, comparison of the results obtained with the different in vitro methods reveal that a prediction of the therapeutic equivalence for locally acting products in the gastrointestinal tract is unlikely based on release profiles obtained in a single drug release experiment. However, results from the study also indicated that a set of individualized biorelevant in vitro test scenarios might be very useful for both demonstrating therapeutic equivalence and selecting the appropriate drug product for a particular patient.
authors.forename: S
authors.initials: S
authors.lastname: Klein
mesh_terms: D002626:Chemistry, Pharmaceutical; D005215:Fasting / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013810:Therapeutic Equivalency
chemical_list: D005765:Gastrointestinal Agents