title: Regional differences in bioavailability of an opioid tetrapeptide in vivo in rats after administration to the respiratory tract.
abstract: TArPP (Tyr-D-Arg-Phe-Phe-NH(2)), 1-10 micromol/kg, was administered to anesthetized rats by nasal microinfusion, intratracheal microinfusion, intratracheal nebulization, aerosol inhalation, and i.v. bolus and infusion. Plasma concentrations of TArPP and its deamidated metabolite were determined by LC-MS-MS. Regional differences in bioavailability (F), first-pass metabolism, and absorption rate were found for TArPP after delivery to the respiratory tract. Absorption was rapid after both pulmonary and nasal administration (t(max) approximately 10-20 min). After nasal microinfusion, F was 52 +/- 9%. For all the pulmonary groups, F was higher (72-114%). First-pass metabolism of TArPP was lower in the lung than in the nasal cavity. It is evident that the pulmonary route is attractive for successful systemic delivery of small, hydrophilic and enzymatic susceptible peptides.
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, BMC, SE-751 23, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Krondahl
authors.forename: Ann
authors.initials: A
authors.lastname: Tronde
authors.forename: Stefan
authors.initials: S
authors.lastname: Eirefelt
authors.forename: Heidi
authors.initials: H
authors.lastname: Forsmo-Bruce
authors.forename: Gunilla
authors.initials: G
authors.lastname: Ekström
authors.forename: Ursula Hultkvist
authors.initials: UH
authors.lastname: Bengtsson
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002463:Cell Membrane Permeability; D004745:Enkephalins / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics*; D018847:Opioid Peptides / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
chemical_list: D000336:Aerosols; D004745:Enkephalins; D009842:Oligopeptides; D018847:Opioid Peptides; C111156:tyrosyl-arginyl-phenylalanyl-phenylaninamide