title: Canine versus in vitro data for predicting input profiles of L-sulpiride after oral administration.
abstract: The objective of this study was to assess the relative usefulness of canine versus in vitro data sets in the prediction of absorption of L-sulpiride (a low permeability compound) from an immediate and an extended release formulation. To reduce species differences on upper gastrointestinal residence times, human and canine data were collected in the fed state. In vitro permeability data (that were additionally confirmed by rat perfusion data) were obtained from the literature. In vitro release data were obtained in media simulating the gastric composition (without and with simultaneous protein digestion) and intestinal composition in the fed state. The results showed that, regardless of the formulation, canine input profiles were vastly different from human profiles at times longer than 2h after administration and led to 2.7 times higher total amount absorbed in dogs. In contrast, reliable in vitro permeability data in combination with in vitro release data collected in biorelevant media led to successful prediction of the human input profile; regardless of the dosage form, simulated and actual mean input profiles differed by less than 20%.
authors.affiliation: School of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, University of Athens, Panepistimiopolis, 157 71 Zografou, Athens, Greece.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Fotaki
authors.forename: Mira
authors.initials: M
authors.lastname: Symillides
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010539:Permeability; D013469:Sulpiride / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D013469:Sulpiride