title: Buccal absorption of propofol when dosed in 1-perfluorobutylpentane to anaesthetised and conscious Wistar rats and Göttingen mini-pigs.
abstract: The purpose of this study was to evaluate whether propofol could be absorbed buccally when administered in semifluorinated alkanes (SFAs), here specifically perfluorobutylpentane (F4H5). This was evaluated in anesthetised and conscious rats and mini-pigs, to measure the relative bioavailability of propofol following buccal administration, but also partly to evaluate the animal models used for this investigation. The absolute bioavailability in the conscious animals was approximately 10% for both species and approximately 50% and 30% in the anesthetised rats and mini-pigs, respectively. This clearly demonstrates that propofol can be absorbed buccally, and F4H5 appears to be a relevant excipient for buccal administration of lipophilic drugs like propofol. The lower absorption in the conscious animals clearly indicates the need for an optimisation of the formulation.
authors.affiliation: Dept. of Anesthesiology and Intensive Care Medicine, University Medical Center, Mannheim, Germany. Electronic address: charalambos.tsagogiorgas@umm.de.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Tsagogiorgas
authors.forename: Sonja
authors.initials: S
authors.lastname: Theisinger
authors.forename: Per
authors.initials: P
authors.lastname: Holm
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
authors.forename: Michael
authors.initials: M
authors.lastname: Quintel
authors.forename: René
authors.initials: R
authors.lastname: Holm
mesh_terms: D000042:Absorption; D000278:Administration, Buccal; D000473:Alkanes / Q000737:chemistry; D000758:Anesthesia / Q000379:methods; D000818:Animals; D001672:Biocompatible Materials; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems; D004848:Epithelium / Q000378:metabolism; D005079:Excipients; D005461:Fluorine / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007633:Keratins / Q000737:chemistry; D010477:Perfusion; D015742:Propofol / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013556:Swine, Miniature
chemical_list: D000473:Alkanes; D001672:Biocompatible Materials; D005079:Excipients; D005466:Fluorocarbons; C533290:perfluorobutylpentane; D005461:Fluorine; D007633:Keratins; D015742:Propofol
keywords: Buccal drug delivery; F4H5; Pig; Propofol; Rats; Semifluorinated alkane