title: [Biopharmaceutics of local anesthetic-cyclodextrin complexes following loco-regional administration].
abstract: In the research of new dosage forms improving the therapeutic index of local anesthetics, we studied cyclodextrins, cyclic oligosaccharides forming soluble inclusion complexes with various lipophilic drugs. Complexes between bupivacaine and hydroxypropyl-B-cyclodextrin, bupivacaine and sulfobutyl ether-7-B-cyclodextrin were studied in vivo, using an epidural and a perineural (sciatic) model, respectively. Biopharmaceutics and pharmacodynamics of bupivacaine were evaluated in the rabbit. In both models, only systemic absorption rate of bupivacaine was decreased upon complexation, not the quantity absorbed. Complexation with cyclodextrins could be a promising drug delivery system to improve the therapeutic index of local anesthetics.
authors.affiliation: Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Université de Rennes I, Faculté des Sciences Pharmaceutiques et Biologiques, 2 avenue du professeur Léon Bernard, F-35043 Rennes Cedex.
authors.forename: G
authors.initials: G
authors.lastname: Dollo
authors.forename: P
authors.initials: P
authors.lastname: Le Corre
authors.forename: J C
authors.initials: JC
authors.lastname: Fréville
authors.forename: F
authors.initials: F
authors.lastname: Chevanne
authors.forename: R
authors.initials: R
authors.lastname: Leverge
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D003505:Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics*; D004304:Dosage Forms; D007268:Injections, Epidural; D007275:Injections, Intravenous; D008969:Molecular Sequence Data; D011817:Rabbits; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins
chemical_list: D000779:Anesthetics, Local; D003505:Cyclodextrins; D004304:Dosage Forms; D047392:beta-Cyclodextrins; C031215:betadex; D002045:Bupivacaine