title: Buccal transport of flecainide and sotalol: effect of a bile salt and ionization state.
abstract: Patients with infrequent attacks of supraventricular arrhythmia may benefit from self administration of antiarrhythmic drugs on an 'as required' basis. The oral cavity is easily accessible and the potential for rapid absorption exists. The effects of ionization state and sodium glycocholate on the ex vivo transport of sotalol and flecainide across porcine buccal mucosa were studied. The permeated amounts at 3 h (Q) and fluxes (J) of sotalol in an aqueous solution at pH 7.4 and 9.0 were similar. At pH 7.4, in contrast to pH 9.0, the addition of 1.0% (w/v) sodium glycocholate decreased Q and J four and five fold. Flecainide base in propylene glycol resulted in a nine and 12 fold higher Q and J as compared with an aqueous solution of flecainide acetate at pH 5.8. The presence of sodium glycocholate reduced the transport rate of the flecainide base. However, Q and J were increased 110 and 75 fold by adding 1.0% (w/v) sodium glycocholate to a solution of flecainide acetate at pH 5.8. Sodium glycocholate seems to be an effective penetration enhancer for the buccal absorption of the more polar ionized form of flecainide in an aqueous solution. Sodium glycocholate does not seem to improve the transport of sotalol.
authors.affiliation: Department of Clinical Pharmacy, St Antonius Hospital, Koekoeslaan 1, 3435, CM, Nieuwegein, The Netherlands. vhm.deneer@farmacie.rhihnhuysen.net
authors.forename: V H M
authors.initials: VH
authors.lastname: Deneer
authors.forename: G B
authors.initials: GB
authors.lastname: Drese
authors.forename: P E H
authors.initials: PE
authors.lastname: Roemelé
authors.forename: J C
authors.initials: JC
authors.lastname: Verhoef
authors.forename: L
authors.initials: L
authors.lastname: Lie-A-Huen
authors.forename: J H
authors.initials: JH
authors.lastname: Kingma
authors.forename: J R B J
authors.initials: JR
authors.lastname: Brouwers
authors.forename: H E
authors.initials: HE
authors.lastname: Junginger
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002610:Cheek; D002851:Chromatography, High Pressure Liquid; D005424:Flecainide / Q000737:chemistry / Q000493:pharmacokinetics*; D006000:Glycocholic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D019999:Pharmaceutical Solutions; D013015:Sotalol / Q000737:chemistry / Q000493:pharmacokinetics*; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D001647:Bile Acids and Salts; D019999:Pharmaceutical Solutions; D013015:Sotalol; D006000:Glycocholic Acid; D005424:Flecainide