title: Rapid Absorption of Dry-Powder Intranasal Oxytocin.
abstract: To probe the suitability of a dry-powder oxytocin formulation containing a carrier (μco™; SNBL, Ltd.) for intranasal (IN) administration to treat post-partum hemorrhage in the developing world. Specifically, to investigate (1) whether IN administration can achieve rapid systemic absorption in cynomolgus monkeys, and (2) whether the formulation exhibits sufficient physical and chemical stability. This study was conducted to support Merck for Mothers, Merck's 10-year global initiative to end preventable maternal deaths.
  
  
  
  A partial-crossover pharmacokinetic (PK) study in cynomolgus monkeys (n = 6) was utilized to compare in vivo absorption of dry-powder IN oxytocin at three dose levels against an IM injection of an aqueous oxytocin formulation. Particle size distribution, delivered dose and chemical assay were monitored over a 12 month stability study.
  
  
  
  IN administration of oxytocin resulted in short (5 min) Tmax and good dose linearity in AUC and Cmax over the dose range tested (10-80 IU per animal). The relative bioavailability (BA) of IN oxytocin to IM injection was approximately 12%. The 80 IU formulation exhibited good physical stability and consistent dosing. After 12 months at 30°C/65%RH, pouched samples retained 86.0% of their original assay value.
  
  
  
  The PK and stability data suggests that IN administration of oxytocin formulated in the μco™ carrier may represent a viable option for rapid systemic absorption in humans and a product compatible with resource-scarce regions.
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA. mikolaj.milewski@merck.com.
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Milewski
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Goodey
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Dinah
authors.initials: D
authors.lastname: Lee
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Rimmer
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Saklatvala
authors.affiliation: TR Division, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Koyama
authors.affiliation: TR Division, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
authors.forename: Mic
authors.initials: M
authors.lastname: Iwashima
authors.affiliation: TR Division, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Haruta
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods*; D008252:Macaca fascicularis; D008297:Male; D065588:Nasal Absorption / Q000187:drug effects / Q000502:physiology*; D010120:Oxytocics / Q000008:administration & dosage / Q000378:metabolism; D010121:Oxytocin / Q000008:administration & dosage* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D010120:Oxytocics; D010121:Oxytocin
keywords: intranasal absorption; peptide; pharmacokinetics; preclinical; stability