부산대학교 도서관

Purpose To probe the suitability of a dry-powder oxytocin formulation containing a carrier ([mu]co[TM]; SNBL, Ltd.) for intranasal (IN) administration to treat post-partum hemorrhage in the developing world. Specifically, to investigate (1 (See CR1)) whether IN administration can achieve rapid systemic absorption in cynomolgus monkeys, and (2 (See CR2)) 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. Methods 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. Results IN administration of oxytocin resulted in short (5 min) T.sub.max and good dose linearity in AUC and C.sub.max 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. Conclusions The PK and stability data suggests that IN administration of oxytocin formulated in the [mu]co[TM] carrier may represent a viable option for rapid systemic absorption in humans and a product compatible with resource-scarce regions.
Author(s): Mikolaj Milewski [sup.1], Adrian Goodey [sup.1], Dinah Lee [sup.1], Eric Rimmer [sup.1], Robert Saklatvala [sup.1], Shuzo Koyama [sup.2], Mic Iwashima [sup.2], Shunji Haruta [sup.2] Author Affiliations: (1) grid.417993.1, 0000000122600793, [...]