Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults
Open accessAbstract
Background The development of oxytocin as a therapeutic agent outside of obstetrics has been hampered by antibody-based assays that lack specificity, leading to inconsistent and incompletely reported pharmacokinetic models to guide drug dosing. This study describes the population plasma pharmacokinetics of intravenous and intranasal oxytocin using a sensitive and specific liquid chromatography-tandem mass spectroscopy (LC/MS) assay.Methods Two studies in healthy adult men and nonpregnant women were performed, the first with intravenous oxytocin 16.7 μg over 1 or 10 min and the second with intravenous oxytocin 13.7 μg over 30 min and, on a separate day, intranasal oxytocin 100 μg (n=24). Venous plasma oxytocin concentration was measured using LC/MS and enzyme-linked immunosorbent assay. Pharmacokinetic parameters were estimated using NONMEM.Results The pharmacokinetics of intravenous oxytocin were well described by a two-compartment model (0% bias, 18% median inaccuracy). The two-compartment model for intranasal oxytocin was characterised by substantial subject-to-subject variability (9% median bias, 47% median inaccuracy). Nasal oxytocin bioavailability was 0.7%. Oxytocin samples assayed with LC/MS were systematically higher than simultaneous samples assayed with enzyme-linked immunosorbent assay.Conclusions The pharmacokinetics of intravenous oxytocin are well described by a two-compartment model. The low bioavailability (<1%) and large intersubject variability in plasma oxytocin after intranasal dosing could partially explain the inconsistent reports of oxytocin efficacy in the clinical literature with this delivery method. A publicly available simulator was created to guide oxytocin dosing in future studies.Clinical trial registration NCT03929367 (Study 1) and NCT05672667 (Study 2).
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Salivary OXT can provide more stable measurements than plasma OXT because it has a longer half-life, whereas plasma OXT fluctuates rapidly due to its 7-min half-life and pulsatile release pattern.
“Unlike plasma OXT, which fluctuates rapidly due to its 7-min half-life (Shafer et al., 2025) and pulsatile release pattern (Baskaran et al., 2017), salivary OXT can provide more stable measurements since it has a longer half-life (Quintana et al., 2018).”
From Music's context-dependent influence on oxytocin, social bonding, and emotion regulation: a systematic review (2026) · cites this paper as Shafer et al., 2025
The Shafer citation is attached specifically to the asserted 7-minute plasma oxytocin half-life, not to the claims about pulsatile release or saliva. The Pharmacokinetic analysis and Table 1 (page unavailable) report plasma model parameters, but searches for “half-life,” “7-min,” and plasma elimination in minutes found no passage stating a 7-minute half-life. (LLM, conf=0.70)
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Chu, T.-H., & Tsai, C.-G. (2026) · Frontiers in cognition · doi:10.3389/fcogn.2025.1678665 · Cited by 8 · see citing works
- Authors
- Shafer, S. L., Ririe, D. G., Miller, S., Curry, R. S., Hsu, D. T., Sullivan, G. M., & Eisenach, J. C.
- Affiliations
- Stanford University (US)
- Wake Forest University (US)
- Tonix Pharmaceuticals (United States) (US)
- Corresponding author
- Shafer, Steven L.
- Venue
- British Journal of Anaesthesia
- Publisher
- Elsevier BV
- Published
- 2025-05
- Volume
- 134
- Issue
- 5
- Pages
- 1513-1522
- ISSN
- 0007-0912 (ISSN-L)
- OpenAlex
- W4408721572
- Cited by
- 5
- References
- 34
- Citations by year
- 2026: 4 · 2025: 1
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- British Journal of Anaesthesia (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (UL1TR001420)
- National Institutes of Health
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- oxytocin, plasma pharmacokinetics, intranasal administration, intravenous administration, bioavailability, interindividual variability, two-compartment model, LC-MS assay, dosing simulation, non-pregnant adults
- MeSH terms
- Administration, Intranasal, Adult, Biological Availability, Chromatography, Liquid, Female, Humans, Male, Middle Aged, Oxytocics, Oxytocin, Tandem Mass Spectrometry, Young Adult, Administration, Intravenous
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