title: Permeation and systemic absorption of R- and S-baclofen across the nasal mucosa.
abstract: Baclofen, an antispasmodic agent that acts as a GABA(B) agonist, resembles phenylalanine in structure and has been reported to be a substrate of the large amino acid transporter 1 (LAT-1). The objective of this study was to investigate the absorption of baclofen across the nasal mucosa both in vitro and in vivo. Baclofen transport was measured across excised bovine olfactory and respiratory mucosae to investigate site-specific uptake of baclofen, and the intranasal bioavailability of R- and S-baclofen was determined in rats. Increasing flux with increasing baclofen donor concentration and the absence of polarized transport was observed in vitro, and similar distribution profiles were observed for both enantiomers following intranasal administration in rats. The absence of stereospecificity in nasal absorption indicates limited involvement of the amino acid or other transporters in the nasal absorption of baclofen.
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Hefei
authors.initials: H
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Schmidt
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Murry
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Donovan
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D001418:Baclofen / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport; D002417:Cattle; D016764:Cell Polarity; D017097:Electric Impedance; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D007536:Isomerism; D008297:Male; D008954:Models, Biological; D009125:Muscle Relaxants, Central / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009125:Muscle Relaxants, Central; D001418:Baclofen