Rapid Absorption of Dry-Powder Intranasal Oxytocin
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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.
KEY WORDSintranasal absorption peptide pharmacokinetics preclinical stability
Area under the curve
Maximum plasma concentration of drug
The diameter of particles where 10% of the population by volume lies below this value
The diameter of particles where half of the population by volume lies below this value
The diameter of particles where 90% of the population by volume lies below this value
Time to maximum plasma concentration of drug
ACKNOWLEDGMENTS AND DISCLOSURES
The authors would like to thank Pastorus Pharma, LLC owner of the license for the dry-powder oxytocin formulation for making it available for Merck-for-Mothers study and sharing pharmacokinetic data of an independent study involving intranasal oxytocin. This research was supported by funding from Merck & Co., Inc., Kenilworth, NJ through its Merck for Mothers program, a $500 Million, 10-year initiative to reducing maternal mortality.
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