Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin

Pharmaceutics

Angela Tseng¹  Ann F. Haynos¹  Suma Jacob¹  Carol B. Peterson¹  Megan DuBois¹  Sunday M. Francis¹ 

[1] Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN 55455, USA;

关键词: oxytocin;    intranasal;    urine;    plasma;    autism;    anorexia;   

DOI  :  10.3390/pharmaceutics14061178

来源: DOAJ

【 摘 要 】

Oxytocin (OT), a mammalian neurohormone associated with social cognition and behavior, can be administered in its synthetic form intranasally (IN) and impact brain chemistry and behavior. IN-OT shows potential as a noninvasive intervention for disorders characterized by social challenges, e.g., autism spectrum disorder (ASD) and anorexia nervosa (AN). To evaluate IN-OT’s efficacy, we must quantify OT uptake, availability, and clearance; thus, we assessed OT levels in urine (uOT) before and after participants (26 ASD, 7 AN, and 7 healthy controls) received 40 IU IN-OT or placebo across two sessions using double-blind, placebo-controlled crossover designs. We also measured uOT and plasma (pOT) levels in a subset of participants to compare the two sampling methods. We found significantly higher uOT and pOT following intranasal delivery of active compound versus placebo, but analyses yielded larger effect sizes and more clearly differentiated pre–post-OT levels for uOT than pOT. Further, we applied a two-step cluster (TSC), blinded backward-chaining approach to determine whether active/placebo groups could be identified by uOT and pOT change alone; uOT levels may serve as an accessible and accurate systemic biomarker for OT dose–response. Future studies will explore whether uOT levels correlate directly with behavioral targets to improve dosing for therapeutic goals.

【 授权许可】

Unknown