Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults.

Summary

Using LC/MS, the authors showed that intravenous oxytocin follows a robust two-compartment model, whereas intranasal oxytocin has very low bioavailability (~0.7%) and high intersubject variability. LC/MS concentrations exceeded ELISA, and a public simulator was released to inform dosing in future studies.

Key Findings

• Intravenous oxytocin PK is well described by a two-compartment model (0% bias; 18% median inaccuracy).
• Intranasal oxytocin shows very low bioavailability (~0.7%) with substantial intersubject variability (47% median inaccuracy).
• LC/MS yields systematically higher oxytocin concentrations than ELISA in simultaneous samples.
• A publicly available dosing simulator was created to inform future oxytocin studies.

Clinical Implications

Intranasal oxytocin is unlikely to achieve therapeutic systemic levels; trials and clinical use should reconsider this route or adjust expectations. Intravenous dosing can be modeled more reliably, and the simulator can guide future dosing strategies.

Limitations

• Small sample size of healthy, nonpregnant adults limits generalizability
• Intranasal PK characterized by high variability; mechanism of low absorption not fully elucidated

Future Directions

Define mechanistic barriers to nasal absorption, evaluate alternative delivery systems or dosing strategies, and test PK–PD links in target populations with the simulator.