title: Inhaled PYY(3-36) dry-powder formulation for appetite suppression.
abstract: OBJECTIVE
  Peptide YY3-36 [PYY(3-36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3-36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.
  
  
  METHODS
  Dry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3-36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3-36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.
  
  
  RESULTS
  Inhalation pharmacokinetic studies showed that plasma exposure was similar for a 2 × higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65 mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4 h, which is similar to IP and subcutaneous delivery routes.
  
  
  CONCLUSIONS
  The pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3-36). Additionally, engineered PYY(3-36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression.
authors.affiliation: a Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kuehl
authors.affiliation: b Pfizer Inc. , Groton , CT , USA , and.
authors.forename: Tracey
authors.initials: T
authors.lastname: Boyden
authors.affiliation: c Bend Research Inc. , Bend , OR , USA.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Dobry
authors.affiliation: a Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.affiliation: c Bend Research Inc. , Bend , OR , USA.
authors.forename: Dwayne T
authors.initials: DT
authors.lastname: Friesen
authors.affiliation: a Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.affiliation: c Bend Research Inc. , Bend , OR , USA.
authors.forename: Brice G
authors.initials: BG
authors.lastname: Murri
authors.affiliation: c Bend Research Inc. , Bend , OR , USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Vodak
authors.affiliation: c Bend Research Inc. , Bend , OR , USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Lyon
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001067:Appetite Depressants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D003890:Desiccation; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D054796:Drug Dosage Calculations; D058995:Dry Powder Inhalers; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019894:Peptide YY / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011208:Powders
chemical_list: D000336:Aerosols; D001067:Appetite Depressants; D003911:Dextrans; D004337:Drug Carriers; D010446:Peptide Fragments; D011208:Powders; D019894:Peptide YY; C061785:peptide YY (3-36)
keywords: Inhalation excipients; PYY; pharmacodynamics; pharmacokinetics; protein/peptide inhalation drug delivery