title: A comparison of the pulmonary bioavailability of powder and liquid aerosol formulations of salmon calcitonin.
abstract: OBJECTIVE
  To compare the pulmonary pharmacokinetics and relative bioavailability of salmon calcitonin delivered as aqueous droplets, pH 6.6 and pH 4.8 with that of a spray dried powder in healthy volunteers.
  
  
  METHODS
  Spray dried powders (1.6 microm [GSD 2.1]) containing 5% by wt. sCal, 6.25% human serum albumin, 73.55% mannitol and 15% citric acid/sodium citrate were prepared using a Buchi model 190 spray drier. Aqueous solutions were prepared by dissolving the spray dried powder at a sCal concentration of 1.25 mg/ml, pH was adjusted using 21 mM sodium hydroxide. Aerosols were delivered as part of a 4 way cross-over study to 16 healthy volunteers. The Nektar pulmonary delivery device was used to deliver the dry powder aerosol. A Salter nebulizer controlled by a Rosenthal dosimeter was used to deliver the aqueous aerosols. Miacalcin injection was used as the subcutaneous control. Dose delivered to the lung was estimated by gamma scintigraphy. Plasma concentrations of sCal were measured using a radioimmunoassay.
  
  
  RESULTS
  Aerosol size distributions were matched, 3.3 microm MMAD and approximately 2.2 GSD. Inhaled flow rates were similar, although not equal, 5.8 and approximately 9.8 l/min respectively for dry powder and liquid inhalations. Lung doses of sCal ranged from 53 to 88 microgm, peripheral lung doses from 25 to 51 microgm. Pharmacokinetic profiles and lung bioavailability relative to subcutaneous injection for all formulations were similar (not statistically significantly different p > 0.05), relative lung bioavailability ranged from 11% to 18%, estimates of relative bioavailability based on peripheral lung dose ranged from 20% to 33%.
  
  
  CONCLUSIONS
  The study showed no difference in pharmacokinetic profiles between the various aerosol dosage forms. pH of the aqueous solutions did not affect kinetics or relative bioavailability.
authors.affiliation: Nektar Therapeutics, San Carlos, CA 94070, USA. aclark@nektar.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Clark
authors.forename: Mei-Chang
authors.initials: MC
authors.lastname: Kuo
authors.forename: Stephen
authors.initials: S
authors.lastname: Newman
authors.forename: Peter
authors.initials: P
authors.lastname: Hirst
authors.forename: Gary
authors.initials: G
authors.lastname: Pitcairn
authors.forename: Matt
authors.initials: M
authors.lastname: Pickford
mesh_terms: D000328:Adult; D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D011208:Powders; D011877:Radionuclide Imaging
chemical_list: D000336:Aerosols; D018927:Anti-Asthmatic Agents; D011208:Powders; C028815:salmon calcitonin; D002116:Calcitonin